Nature Reviews Molecular Cell Biology Research Articles

Publication trends in nature reviews molecular cell biology: A scientometric analysis based on scopus database

Nature Review Molecular Cell Biology is one of the most prestigious journals in molecular and cellular biology. The focus of this research study is to use scientometric analysis to look at the publication trends of Nature Reviews Molecular Cell Biology. The data were collected from the Scopus database covering 20 years. The present study covers the years 2000–2019, with 3397 articles published during the study period. The study concentrates on publication trends, highly productive authors, collaborative institutions, countries, and highly cited publications. The analysis of the study revealed that 2001 witnessed the highest number of publications. Heinrichs, A. was ranked as the most productive author, contributing a total of 165 articles. The United States of America and the United Kingdom have the most international collaboration players. The maximum number of publications published in the review was 1307(38.47%) of the publication. The article “Understanding the ErbB Signaling Network by Yarden, Y., and Sliwkowski, M.X.” has the most citations and was published as a review. This scientometric study will benefit researchers in the field of molecular cell biology because it will highlight the amount of literature published during the study period and worldwide collaboration among researchers.

Recurrent Germline Variant in the Cohesin Complex Gene RAD21 Predisposes Children to Lymphoblastic Leukemia and Lymphoma

Introduction: Cohesin complex genes are commonly mutated in cancer particularly in myeloid malignancies. Yet patients with germline mutations in cohesin genes, leading to cohesinopathies like Cornelia-de-Lange syndrome (CdLS) are generally not known to be tumor-prone. The complex plays a major role in chromosome alignment and segregation (Uhlmann, Nature Reviews Molecular Cell Biology, 2016), homologous recombination-driven DNA repair (Ström et al., Molecular Cell, 2004) and regulation of gene expression (Busslinger et al., Nature, 2017). To deepen the understanding of cohesin variants in cancer predisposition, we performed TRIO Sequencing in two independent pediatric cancer cohorts. Thereby, we identified a novel recurrent heterozygous germline variant in the cohesin gene RAD21 not described in CdLS patients , located in the binding domain of the cofactors WAPL and PDS5B .Methods: Whole exome sequencing (WES) in a TRIO (child-parent datasets) setting was carried out in two independent, unselected cancer cohorts (TRIO-D, n=158 (Wagener et al., European Journal of Human Genetics, 2021) and TRIO-DD, n=60). To investigate the oncogenic potential of the novel RAD21 variant molecular and functional assessment was performed focusing on potential implications on the complex.Results: The newly identified RAD21 variant at amino acid position 298 resulting in a Proline to Serine (p.P298S) and a Proline to Alanine exchange, respectively, (p.P298A) is only rarely mutated in the general population (gnomAD database n=118,479; RAD21 p.P298S MAF <10 -6 and RAD21 p.P298A MAF <10 -5). While both patients did not show any signs of CdLS, they both have a remarkable family history of cancer. Patient 1 (13y) was diagnosed with T-cell acute lymphoblastic leukemia (T-ALL) whose father had died from breast cancer (41y), while patient 2 (2y) presented with precursor B-cell lymphoblastic lymphoma (pB-LBL) whose uncle had died from pediatric cancer of unknown subtype (8y).To assess the influence of RAD21 p.P298S/A on the binding capacity of the complex, RAD21 variants and the wildtype (WT) were cloned and transfected into HEK293T cells, respectively. Immunoprecipitation analysis of RAD21 with the cofactors WAPL and PDS5B showed no differential binding between the WT and the variants, suggesting that RAD21 p.P298S/A does not impact the formation of the complex.Nevertheless, on a transcriptional level 83 genes were significantly differentially expressed in RAD21 p.P298S and p.P298A compared to the wildtype (fc>1.5, adj. p-value <0.05) with enrichment of genes in p53 signaling pathways. We further observed an increased number of γH2AX and 53BP1 co-localized foci compared to the WT (p≤0.01; Student's t-test). In line, following ionizing radiation, primary patients' samples showed increased cell cycle arrest at G2/M cell-cycle stage compared to a healthy control (p.P298S: p=0.0049 [6Gy]; p=0.0026 [10Gy]; p.P298A: p=0.0054 [6Gy]; p=0.0006 [10Gy]; Student's t-test).For cross-validation of the germline variant RAD21 p.P298S/A and its potential role in pediatric lymphoblastic malignancies, we analysed a third cohort of 150 children with relapsed ALL (IntReALL) for RAD21 p.P298S/A. We again identified RAD21 p.P298A in a boy (12y) with B-cell precursor acute lymphoblastic leukemia. To compare our data to a non-pediatric cancer setting, a cohort of 2300 young adults (<51 years) with cancer was mined (MASTER program). Here, one patient carrying RAD21 p.P298A with a solid tumor was identified. Therefore, amongst all cohorts, RAD21 p.P298S/A was found to be enriched in pediatric vs. adult cancers (3/479 vs. 1/2299; Fisher's exact test; p=0.018).Conclusion: Taken together, we present for the first time the potential role of RAD21 germline variants in pediatric lymphoblastic malignancies. This may shed new light on the many roles of the cohesin complex and its implication outside the typical syndromal presentation. DisclosuresNo relevant conflicts of interest to declare.

Genetic techniques for plant breeding

Food Science and TechnologyVolume 35, Issue 3 p. 52-54 FeaturesFree Access Genetic techniques for plant breeding First published: 16 September 2021 https://doi.org/10.1002/fsat.3503_13.xAboutSectionsPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Wayne Martindale and Craig Duckham explore the barriers to the adoption of new genetic breeding techniques that facilitate the selection of desired traits to improve the quality and quantity of food products. Conventional plant breeding Human societies have been engaged in plant breeding since the beginning of agriculture by selecting plants found to be economically or aesthetically desirable and controlling the mating of selected individuals. Genetic variation has had a major impact on one of the UK's most successful crops, wheat. The straw yield, grain yield and quality of wheat has constantly changed over time to meet the market requirements of consumers as well as to utilise plant nutrients and plant protection applications as efficiently as possible. The Broadbalk Experiment at Rothamsted provides a living lab of these interactions and changes over 150 years. What is striking is that most of these improvements to date have been carried out by observable traits and long-term breeding programmes. We are now on the cusp of a revolution, where observational selection can work with new genetic techniques to provide more targeted outcomes for a 21st century food system1-3. Genetic modification of foods In the 1970s, the development of genetic engineering or genetic modification (GM) methods using recombinant-DNA technology offered the potential to enhance agri-food industry breeding programmes for crops, ornamental plants and animals. The aim was to speed up selection of genetic traits rather than relying on classical breeding programmes that selected from randomised mutations induced using radiation or chemicals, followed by recombination between varieties or breeds. Genetically modified organisms (GMOs) are officially defined in EU legislation as ‘organisms in which the genetic material (DNA) has been altered in a way that does not occur naturally by mating or natural recombination’. We are now on the cusp of a revolution, where observational selection can work with new genetic techniques to provide more targeted outcomes for a 21st century food system. One of the first applications of genetic engineering was the use of transgenic bacteria (Pseudomonas syringae) to reduce ice nucleation on the leaves of frost-susceptible crop plants. This was developed as a product called Frostban but was never marketed because of controversy about its safety4. Since then the most commonly commercialised GMOs have been soybean, maize, cotton and oilseed rape. The greatest commercial impact has been observed for insect resistance and herbicide tolerance, which are single, specific gene transfers that provide plant protection5. The approach can also be used for many other traits, such as enhancing the nutritional value of crops and livestock. These developments have all been achieved by introducing genetic material from unrelated species (transgenics) using Agrobacterium tumefaciens-mediated transformation and biolistic or ‘gene gun’ methods. They require expensive selection programmes, which use herbicide, bioluminescence or antibiotic resistance marker genes to identify the successful transfer of the transgene constructs into new crops or livestock. More recently, new plant breeding techniques, known as gene editing, have been developed, which allow much faster and more precise changes to be made within plant DNA than can be achieved by conventional breeding methods. DNA modifications resulting from gene editing can vary in scale from altering a single base, to inserting or removing one or more genes. Gene editing approaches do not use the marker gene technique, which is the basis of many safety concerns around GMOs, and are being considered for classification as conventional plant breeding techniques that sit outside the current EU GMO legislation. Gene editing uses a group of bacterial enzymes called CRISPR Associated Proteins, one of which (Cas-9) has been demonstrated to identify specific gene sequences in plants and animals that then can be cut, modified or switched on or off (gene silencing) by the Cas-9 enzyme6. There is no transgene construct nor typically a need for a selection marker; the Cas-9 approach uses metabolic means to edit genetic codes, it quite literally provides a metabolic toolbox that can target and modify specific existing genetic sequences. It provides the means to engineer the existing metabolism of crops and livestock with the same precision as that of transgenic methods, without the need to insert foreign DNA. Engaging food stakeholders Opposition to the development of transgenic organisms for use in foods and beverages has created a tortuous path for agricultural R&D pipelines developing new crop varieties, animal breeds and ingredients from microbes. It has also damaged consumer confidence in these GM products, particularly in Europe. Research and development in recent years has led to new crop varieties and livestock breeds using (1) rapid selection technologies and (2) scaling opportunities for market entry for the most beneficial products. However, processors and manufacturers of foods and beverages have often not been fully engaged in exploring the potential of such products within their development programmes. This has resulted in barriers to the adoption of these new breeding techniques in the supply chain and concerns about consumer assurance, which is at the heart of any food supply system. The potential benefits of using genetic techniques for product development are often not widely demonstrated to manufacturers or consumers. As a result, there is a lack of assurance, acceptance and application of ingredients produced by these methods, some of which already have a significant legacy of being used in the brewing and baking industries7. Even so, there are some excellent examples of customer engagement by enzyme and ingredient companies. An important demonstrator has been Novozymes’ use of Life Cycle Assessment to measure the benefits of using biotechnology across several products including nutrients and detergents, where standardised validation is in place for GM products8. However, these initiatives to date have been limited and have not had sufficient traction in research or policy arenas. Golden Rice An example of a missed opportunity to communicate the potential benefits of GM technology to consumers is provided by Golden Rice, which accumulates Provitamin A in the grain as a result of genetic transformation9 and has enormous humanitarian potential in reducing blindness (500,000 children per year) and infant mortality (2-3m deaths per year)10. Although the prototype for Golden Rice was developed some 20 years ago, regulatory requirements and associated costs are still standing in the way of its deployment by farmers. Scientific progress in the public sector has thus become detached from product development and the population at large is not benefiting from that progress9. GM in the food chain An example, which demonstrates the potential extent of the issue, is the presence of GM feed in animal production food chains, even though all livestock products are classed as GM free in Europe. This is because the modified genetic attribute (e.g. for herbicide resistance) is not present in the final food product despite it benefitting significantly from other GM materials in the supply chain. This is an important emergent issue in the food industry with respect to custody of responsible data use associated with products. In the case of herbicide resistance, there have been a number of recent cases at the level of State legislature in the USA that have tested this supply chain custody for GM use in foods11. The custody of supply chain data is now more robust than ever and it has been tested with respect to allergen management, financial irregularities, food fraud and so on. The feed example shows the operating environment has moved on regarding use of GM in foods – without a wider discussion of the potential to realise other opportunities and to consider ongoing challenges related to the use of GM in the food system. We can take this chain of custody further, of course, and for example include assays that utilise GM enzyme technology to measure speciation for authenticity and food fraud analysis. Food production would be seriously disrupted if GM free is a requirement for the whole supply chain. These circumstances could be counterproductive to the point of stifling innovation in the food and beverage industries. GM vs gene editing In the UK and the EU, organisms produced using gene editing techniques are classed as GMOs because the precautionary principle is applied, irrespective of the assessment of safety considerations and measurable impacts on the environment and food safety. In the EU, this position is currently under review because other countries, e.g. Japan12, base their food safety legislation on the safety of the end products of breeding programmes and not by the means the genetic changes are brought about. This is all highly controversial because food producers do not want to arouse the same suspicions about gene edited products as have been associated with transgenic products. It is important to consider CRISPR as a suite of gene editing tools that are relevant for tackling the problems of our future food system. Globalisation has seen the rise of agricultural economies in low and middle income countries that have transformed our worldview of agriculture and food. Climate change, coupled with changes in food production methods and a growing population have brought new issues that necessitate a more circular food economy and net carbon neutral outcomes. The 17 UN Sustainable Development Goals clearly build on eradicating hunger and poverty by aligning to fairness and equity in the use of global resources. They will not be achievable without the successful integration of accessible and assured technologies, such as gene editing, to deliver the necessary advances in food production and processing. Conclusions Food and beverage manufacturers are the ‘missing middle’ between agricultural production and retail/consumers; if they are not engaged in attempts to launch new products or ingredients using new genetic technologies, the opportunities will often be limited in scope. A constructive dialogue is needed to engage food manufacturers and consumers with the potential benefits from these technologies, which can help us to address some of the major challenges for the future food system. Gene editing, in particular, offers a fast, precise technique for making changes to the genome. Changes to European legislation governing gene editing could facilitate the introduction of this technology on a much wider basis, provided that consumers are involved and engaged with the potential benefits. Dr Wayne Martindale, Associate Professor in Food Insights and Sustainability at the National Centre for Food Manufacturing, University of Lincoln. Wayne leads the Food Insights and Sustainability Research agenda at NCFM, working with food and beverage manufacturers to deliver a carbon neutral or carbon zero food system. He's a Fellow of IFST and a science champion for nutrition for the STFC Food+ Network, which supports Early Career Researchers. Email wmartindale@lincoln.ac.uk Craig Duckham, Director of CD R&D Consultancy Services Ltd. Craig provides independent advice to businesses on food ingredients’ technologies. He obtained a PhD in Plant Physiology from the University of Nottingham and is a Fellow of IFST. Craig has over 20 years of technical development experience and has published on topics including plant metabolism, microencapsulation and the alternative uses of Brewer's yeast. Email craig.duckham@cdrnd.co.uk Web cdrnd.co.uk References 1Gracia-Romero, A., Kefauver, S.C., Fernandez-Gallego, J.A., Vergara-Díaz, O., Nieto-Taladriz, M.T., Araus, J.L. 2019. UAV and ground image-based phenotyping: a proof of concept with durum wheat. Remote Sensing 11: 1244Google Scholar 2Singh, D., Wang, X., Kumar, U., Gao, L., Noor, M., Imtiaz, M., Singh, R.P., Poland, J. 2019. High-throughput phenotyping enabled genetic dissection of crop lodging in wheat. Frontiers in Plant Science 10: 394Google Scholar 3Ye, H., Huang, W., Huang, S., Cui, B., Dong, Y., Guo, A., Ren, Y., Jin, Y. 2020. Recognition of banana Fusarium wilt based on UAV remote sensing. Remote Sensing 12: 938Google Scholar 4Van Brunt, J. 1987. Environmental release: a portrait of opinion and opposition. Nature Biotechnology 5: 558– 563Google Scholar 5Gilbert, N., 2013. Case studies: a hard look at GM crops. Nature 497: 24Google Scholar 6Strzyz, P. 2020. CRISPR–Cas9 wins Nobel. Nature Reviews Molecular Cell Biology 21: 714Google Scholar 7Nielsen, P.H., Oxenbøll, K.M., Wenzel, H. 2007. Cradle-to-gate environmental assessment of enzyme products produced industrially in Denmark by Novozymes A/S. The International Journal of Life Cycle Assessment 12: 432Google Scholar 8LCA from cradle to grave. https://www.novozymes.com/en/about-us/sustainability/lcaGoogle Scholar 9Al-Babili, S., Beyer, P. 2005. Golden Rice – five years on the road–five years to go? Trends in Plant Science 10: 565– 573Google Scholar 10Golden Rice Humanitarian Board. http://www.goldenrice.org/Content2-How/how4_regul.phpGoogle Scholar 11Adenle, A.A., Morris, E.J., Murphy, D.J., Phillips, P.W.B., Trigo, E. et al. 2018. Rationalizing governance of genetically modified products in developing countries. Nature Biotechnology 36: 137– 139Google Scholar 12Tsuda, M., Watenabe, K.N., Ohsawa, R. 2019. Regulatory Status of Genome-Edited Organisms Under the Japanese Cartagena Act. Frontiers in Bioengineering and Biotechnology 7: 387; https://doi.org/10.3389/fbioe.2019.00387Google Scholar Volume35, Issue3September 2021Pages 52-54 ReferencesRelatedInformation

HATs off for the Lasker awardees.

Nature Reviews Molecular Cell Biology congratulates the winners of the 2018 Lasker Foundation Awards.

Publisher correction: The essential kinase ATR: ensuring faithful duplication of a challenging genome.

Nature Reviews Molecular Cell Biology 18, 622–636 (2017) In the original article, references 36, 68 and 110 contained mistakes. These have now been corrected in the HTML and PDF versions of the article.

Modeling the UPR in neurodegenaration

Event Abstract Back to Event Modeling the UPR in neurodegenaration Georgia Theocharopoulou1* and Catherine Bobori1* 1 Ionian University, Informatics, Greece Neurodegenerative diseases are characterized by problems in protein synthesis causing misfolded proteins. Unfolded protein response (UPR), a cellular stress response, has a role in the accumulation of unfolded or misfolded proteins, using four basic functions. In Huntington’s Disease it has been observed that there is an amount of misfolded huntingtin in the cytoplasm, as well as reduced amount of molecular chaperones leading to the reduction of their role. Molecular chaperones, are proteins, which act in a dynamic manner in cases of stress or misfolding, and are involved in the quality control system of the cell. Age –related changes in the mechanisms of chaperones action, lead to the eventual failure of protein defense system. Deciphering protein-protein interactions will help to the identification of specific causal pathways in protein aggregation and better understanding of the unfolded protein response. This work will use neuroinformatics’ methods in order to design in vitro techniques that will examine the density of chaperones in HD cells, as well as the effectiveness of the UPR. The elucidation of the complex response of UPR will help to test new therapeutic strategies against neurodegenerative diseases. References Saibil, Helen. "Chaperone machines for protein folding, unfolding and disaggregation." Nature reviews Molecular cell biology 14.10 (2013): 630-642. Kalathur, Ravi Kiran Reddy, et al. "The unfolded protein response and its potential role in Huntington ́s disease elucidated by a systems biology approach." F1000Research 4 (2015). Mittal, Jeetain, and Robert B. Best. "Dependence of protein folding stability and dynamics on the density and composition of macromolecular crowders." Biophysical journal 98.2 (2010): 315-320. Kumaraswamy, Priyadharshini, Swaminathan Sethuraman, and Uma Maheswari Krishnan. "Designing In Vitro Strategies and In Vivo Models for Alzheimer's Disease-Promises & Challenges." Current Alzheimer Research 11.6 (2014): 588-607. Braakman, Ineke, and Daniel N. Hebert. "Protein folding in the endoplasmic reticulum." Cold Spring Harbor perspectives in biology 5.5 (2013): a013201. Bortolussi, Luca, and Alberto Policriti. "Modeling biological systems in stochastic concurrent constraint programming." Constraints 13.1-2 (2008): 66-90. Kaufman, Randal J. "Orchestrating the unfolded protein response in health and disease." The Journal of clinical investigation 110.10 (2002): 1389-1398. Wetie, Armand G. Ngounou, et al. "Protein–protein interactions: switch from classical methods to proteomics and bioinformatics-based approaches." Cellular and Molecular Life Sciences 71.2 (2014): 205-228. Keywords: Neurodegenaration, Huntington Disease, Computational models, chaperones, unfolded protein response (UPR) Conference: Neuroinformatics 2016, Reading, United Kingdom, 3 Sep - 4 Sep, 2016. Presentation Type: Poster Topic: Computational neuroscience Citation: Theocharopoulou G and Bobori C (2016). Modeling the UPR in neurodegenaration. Front. Neuroinform. Conference Abstract: Neuroinformatics 2016. doi: 10.3389/conf.fninf.2016.20.00066 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 31 May 2016; Published Online: 18 Jul 2016. * Correspondence: Mrs. Georgia Theocharopoulou, Ionian University, Informatics, CORFU, 49100, Greece, zeta.theo@ionio.gr Mrs. Catherine Bobori, Ionian University, Informatics, CORFU, 49100, Greece, tero-nana@windowslive.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Georgia Theocharopoulou Catherine Bobori Google Georgia Theocharopoulou Catherine Bobori Google Scholar Georgia Theocharopoulou Catherine Bobori PubMed Georgia Theocharopoulou Catherine Bobori Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Erratum: Transcriptional regulation of hepatic lipogenesis

Nature Reviews Molecular Cell Biology 16, 678–689 (2015) In the original article, the reference citation (reference 71) in the following sentence on page 683 was incorrect: “Under hyperglycaemic and hypoinsulinaemic conditions, LXRs maintain the ability to upregulate the expression of glycolytic andlipogenic enzymes, including glucokinase, SREBP1C, ChREBPα and ChREBPβ”.

Erratum: Three-dimensional genome architecture: players and mechanisms

Nature Reviews Molecular Cell Biology 16, 245–257 (2015) In the original article, the following sentence was incorrect: “Histone marks associated with enhancers, such as histone 3 Lys4 monomethylation (H3K4me1), and with transcription repression, such as histone 3 Lys9 trimethylation (H3K9me3), werealso enriched at TAD boundaries.

Erratum: Slowly (translate) but surely (translocate)

Nature Reviews Molecular Cell Biology http://dx.doi.org/10.1038/nrm3921 (2015) The last sentence of the penultimate paragraph stated that the efficiency of translation decreased when a REST sequence was changed to optimal codons. It should have stated that the efficiency of translocation decreased in this setting.

Erratum: The lipid trade

Nature Reviews Molecular Cell Biology 15, 79 (2014) The above article referred to the protein Snf1, but it should have referred to Sfh1 instead, in all places. This has been corrected online. The author apologizes for any confusion caused to readers.

Erratum: The amyloid state and its association with protein misfolding diseases

Nature Reviews Molecular Cell Biology 15, 384–396 (2014) In the legend of figure 2 of the above article (page 388), the sentence “The spacing between polypeptide chains along the fibril axis is constant to a good approximation even for very different polypeptide sequences, a generic property arisingfrom the common inter-side chain hydrogen bonding constraints (orange line in part b).

Erratum: A day in the life of the spliceosome

Nature Reviews Molecular Cell Biology 15, 108–122 (2014) In table 1 (page 116) of the above article, the secondary structure of the snRNAs (small nuclear RNAs) for the U4–U6 di-snRNP (small nuclear ribonucleoprotein) was incorrect. This has now been rectified in the online version of the article. Nature Reviews Molecular Cell Biology apologizes for any confusion caused to readers.

Erratum: Biogenesis and homeostasis of chloroplasts and other plastids

Nature Reviews Molecular Cell Biology 14, 787–802 (2013) In the above article, figure 4 (page 794) had an incorrect label, which indicated that plastid DNA-encoded proteins are co-transcriptionally targeted to thylakoids, whereas targeting actually occurs co-translationally. Also, on pages 796–798 of the article, there were spelling mistakes in the definitions of PDV1 and COP1, which should be PLASTID DIVISION 1 and CONSTITUTIVE PHOTOMORPHOGENESIS 1, respectively.

Erratum: Capping protein regulators fine-tune actin assembly dynamics

Nature Reviews Molecular Cell Biology 15, 677–689 (2014) On page 684 of the above article, there was a mistake in Figure 3b: the PH domain of CARMIL preferentially binds to monophosphorylated membrane lipids rather than to PtdIns(3)P, PtdIns(3,4)P2 or PtdIns(3,4,5)P3. This has been corrected online.We apologize for any confusion caused to readers.

Erratum: Endocycles: a recurrent evolutionary innovation for post-mitotic cell growth

Nature Reviews Molecular Cell Biology 15, 197–210 (2014) In the above article, reference 168 (page 210) was incorrectly cited. The citation appeared as: Tamori, Y. & Deng, W. M. Cell competition and its implications for development and cancer. J. Genet. Genom. 38, 483–495 (2011). The correct citation is: Tamori, Y.

Growth and development of the postsynaptic active region of an excitatory glutemergic synapse: An integrated model

Event Abstract Back to Event Growth and development of the postsynaptic active region of an excitatory glutemergic synapse: An integrated model Venkateswaran Nagarajan1*, Vishal Raghu2, Ganesh Ranganath Chandrasekar2 and Kapardi Mallampalli2 1 Waran Research Foundation, India 2 Waran Research Foundation, India In an excitatory dendrite, the genesis of a synapse begins with a dendritic filopodium making a tactile contact with a presynaptic bouton due to growth initiated by BDNF-TrkB mediated actin polymerisation in the filopodium. During its development, the postsynaptic spine head enlarges and the apical periphery becomes the site for synaptic activity. The assimilation of the postsynaptic density (PSD) in this site marks the begining of postsynaptic development, which subsequently develops to become the kernel of synaptic activity and provides a scaffolding that houses the receptors, CAMs and the various growth related protiens, the study of which is incipient. The morphology of PSD and the potentiation of an excitatory synapse have a relationship that is synergic in nature. Our petrinet based model aims to trace the genesis and the morphological modifications undergone by the PSD of the postsynaptic region of an excitatory glutemergic synapse, begining from the genesis of an excitatory synapse, through the various stages of its development. The chief signalling pathways include those triggered by NMDA and AMPA receptors, Trkb-BDNF, Integrin and Epherin and the ionotropic receptors that are the focus of our study are NMDA and AMPA where NMDA acts as a ligand gated ion channel for Ca2+ and AMPA for Na+. In our model, we have proposed a mechanism that controls the shape of the postsynaptic region of synaptic activity as a function of the positions of neuriligin (Nlg-1) molecules on the PSD platforms through a method of zonal actin polymerization (ZAP). Acoording to our hypothesis, the polymerization of actin occurs in individual "zones" beneath the PSD. The zones which underlie the Nlg-1 pillars or, are in their vicinity, have inhibitted growth due to excess opposing force offered by the PSD, in comparision with zones devoid of Nlg-1 influence. Depending upon the positions of the Nlg-1 molecules near the centre and/or at the ends of the PSD, a plethora of shapes starting from a convex spherical spine head to a concave cup-shaped one can be obtained. Furthermore, we intend to incorporate a system of retrograde signalling mediated the generation and release of retrograde messangers which is instigated by Ca2+ influx in the postsynapse. The activation of the PLC pathway by neurotrophins produces DAG from the lipids upon hydrolysis. DAG then generates the endocannabinoid receptor messengers upon interaction with Ca2+. References Venkateswaran, Nagarajan, Sudarshan Sekhar, Thiagarajan Thirupatchur Sanjayasarathy, Sharath Navalpakkam Krishnan, Dinesh Kannan Kabaleeswaran, Subbu Ramanathan, Narendran Narayanasamy, Sharan Srinivas Jagathrakshakan, and S. R. Vignesh. "Energetics based spike generation of a single neuron: simulation results and analysis." The link between brain energy homeostasis and neuronal activity (2012): 104. Dillon, Christian, and Yukiko Goda. "The actin cytoskeleton: integrating form and function at the synapse." Annu. Rev. Neurosci. 28 (2005): 25-55. Rangamani, Padmini, Marc-Antoine Fardin, Yuguang Xiong, Azi Lipshtat, Olivier Rossier, Michael P. Sheetz, and Ravi Iyengar. "Signaling network triggers and membrane physical properties control the actin cytoskeleton-driven isotropic phase of cell spreading." Biophysical journal 100, no. 4 (2011): 845-857. Chua, John JE, Stefan Kindler, Janina Boyken, and Reinhard Jahn. "The architecture of an excitatory synapse." Journal of cell science 123, no. 6 (2010): 819-823. Squire, Larry R., ed. Fundamental neuroscience. Academic Press, 2013. Choquet, Daniel, and Antoine Triller. "The role of receptor diffusion in the organization of the postsynaptic membrane." Nature Reviews Neuroscience 4, no. 4 (2003): 251-265. Bressloff, Paul C., and Berton A. Earnshaw. "A dynamic corral model of receptor trafficking at a synapse." Biophysical journal 96, no. 5 (2009): 1786-1802. Bennett, Max R., Les Farnell, and William G. Gibson. "A model of NMDA receptor control of F-actin treadmilling in synaptic spines and their growth." Bulletin of mathematical biology 73, no. 9 (2011): 2109-2131. Mogilner, Alex, and Leah Edelstein-Keshet. "Regulation of actin dynamics in rapidly moving cells: a quantitative analysis." Biophysical journal 83, no. 3 (2002): 1237-1258. Pollard, Thomas D., and Gary G. Borisy. "Cellular motility driven by assembly and disassembly of actin filaments." Cell 112, no. 4 (2003): 453-465. Pollard, Thomas D., Laurent Blanchoin, and R. Dyche Mullins. "Molecular mechanisms controlling actin filament dynamics in nonmuscle cells." Annual review of biophysics and biomolecular structure 29, no. 1 (2000): 545-576. Wegner, Adam M., Caroline A. Nebhan, Lan Hu, Devi Majumdar, Kristen M. Meier, Alissa M. Weaver, and Donna J. Webb. "N-wasp and the arp2/3 complex are critical regulators of actin in the development of dendritic spines and synapses." Journal of biological chemistry 283, no. 23 (2008): 15912-15920. Mondin, Magali, Virginie Labrousse, Eric Hosy, Martin Heine, Béatrice Tessier, Florian Levet, Christel Poujol, Christophe Blanchet, Daniel Choquet, and Olivier Thoumine. "Neurexin-neuroligin adhesions capture surface-diffusing AMPA receptors through PSD-95 scaffolds." The Journal of Neuroscience 31, no. 38 (2011): 13500-13515. Derkach, Victor A., Michael C. Oh, Eric S. Guire, and Thomas R. Soderling. "Regulatory mechanisms of AMPA receptors in synaptic plasticity." Nature Reviews Neuroscience 8, no. 2 (2007): 101-113. Pantaloni, Dominique, Terrell L. Hill, Marie-France Carlier, and Edward D. Korn. "A model for actin polymerization and the kinetic effects of ATP hydrolysis." Proceedings of the National Academy of Sciences 82, no. 21 (1985): 7207-7211. Shen, Kang, and Christopher W. Cowan. "Guidance molecules in synapse formation and plasticity." Cold Spring Harbor perspectives in biology 2, no. 4 (2010): a001842. Tada, Tomoko, and Morgan Sheng. "Molecular mechanisms of dendritic spine morphogenesis." Current opinion in neurobiology 16, no. 1 (2006): 95-101. Gambrill, Abigail C., and Andres Barria. "NMDA receptor subunit composition controls synaptogenesis and synapse stabilization." Proceedings of the National Academy of Sciences 108, no. 14 (2011): 5855-5860. Assaife-Lopes, Natália, Vasco C. Sousa, Daniela B. Pereira, Joaquim A. Ribeiro, and Ana M. Sebastião. "Regulation of TrkB receptor translocation to lipid rafts by adenosine A2A receptors and its functional implications for BDNF-induced regulation of synaptic plasticity." Purinergic signalling (2013): 1-17. Gauthier-Campbell, Catherine. "Regulation of filopodia dynamics is critical for proper synapse formation." (2008). Nikolov, Dimitar B., Kai Xu, and Juha P. Himanen. "Eph/ephrin recognition and the role of Eph/ephrin clusters in signaling initiation." Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics 1834, no. 10 (2013): 2160-2165. Patapoutian, Ardem, and Louis F. Reichardt. "Trk receptors: mediators of neurotrophin action." Current opinion in neurobiology 11, no. 3 (2001): 272-280. Minichiello, Liliana. "TrkB signalling pathways in LTP and learning." Nature Reviews Neuroscience 10, no. 12 (2009): 850-860. Huang, Eric J., and Louis F. Reichardt. "Trk receptors: roles in neuronal signal transduction*." Annual review of biochemistry 72, no. 1 (2003): 609-642. Goswami, Chandan. "Structural and functional regulation of growth cone, filopodia and synaptic sites by TRPV1." Commun Integr Biol 3, no. 6 (2010): 614-618. Ziff, Edward B. "TARPs and the AMPA receptor trafficking paradox." Neuron 53, no. 5 (2007): 627-633. Nakagawa, Terunaga. "The biochemistry, ultrastructure, and subunit assembly mechanism of AMPA receptors." Molecular neurobiology 42, no. 3 (2010): 161-184. Cokic, Barbara. "Regulation of AMPA receptor function and synaptic localization by stargazin and PSD-95." PhD diss., lmu, 2009. Shanks, Natalie F., Tomohiko Maruo, Anthony N. Farina, Mark H. Ellisman, and Terunaga Nakagawa. "Contribution of the global subunit structure and stargazin on the maturation of AMPA receptors." The Journal of Neuroscience 30, no. 7 (2010): 2728-2740. Louros, Susana Ribeiro dos. "The Role of Transmembrane AMPA Receptor Regulatory Proteins (TARPs) in Synapse Remodeling and Homeostatic Plasticity." (2012). Martin, Jean-Luc, and Charles Finsterwald. "Cooperation between BDNF and glutamate in the regulation of synaptic transmission and neuronal development." Commun Integr Biol 4, no. 1 (2011): 14-16. Zhu, Ping Jun, and David M. Lovinger. "Retrograde endocannabinoid signaling in a postsynaptic neuron/synaptic bouton preparation from basolateral amygdala." The Journal of neuroscience 25, no. 26 (2005): 6199-6207. Hibbert, Andrew P., Bianca MR Kramer, Freda D. Miller, and David R. Kaplan. "The localization, trafficking and retrograde transport of BDNF bound to p75NTR in sympathetic neurons." Molecular and Cellular Neuroscience 32, no. 4 (2006): 387-402. Sugiura, Takayuki, Sachiko Kondo, Akihiro Sukagawa, Shinji Nakane, Akira Shinoda, Kiyoko Itoh, Atsushi Yamashita, and Keizo Waku. "2-Arachidonoylgylcerol: a possible endogenous cannabinoid receptor ligand in brain." Biochemical and biophysical research communications 215, no. 1 (1995): 89-97. Stella, Nephi, Paul Schweitzer, and Daniele Piomelli. "A second endogenous cannabinoid that modulates long-term potentiation." Nature 388, no. 6644 (1997): 773-778. Wilson, Rachel I., and Roger A. Nicoll. "Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses." Nature 410, no. 6828 (2001): 588-592. Magby, Jason P., Caixia Bi, Zhe-Yu Chen, Francis S. Lee, and Mark R. Plummer. "Single-cell characterization of retrograde signaling by brain-derived neurotrophic factor." The Journal of neuroscience 26, no. 52 (2006): 13531-135. Mufson, Elliott J., Jeffrey S. Kroin, Timothy J. Sendera, and Teresa Sobreviela. "Distribution and retrograde transport of trophic factors in the central nervous system: functional implications for the treatment of neurodegenerative diseases." Progress in neurobiology 57, no. 4 (1999): 451-484. Takenawa, Tadaomi, and Shiro Suetsugu. "The WASP–WAVE protein network: connecting the membrane to the cytoskeleton." Nature reviews Molecular cell biology 8, no. 1 (2007): 37-48. Shen, Kang, and Christopher W. Cowan. "Guidance molecules in synapse formation and plasticity." Cold Spring Harbor perspectives in biology 2, no. 4 (2010): a001842. Ziv, Noam E., and Stephen J. Smith. "Evidence for a role of dendritic filopodia in synaptogenesis and spine formation." Neuron 17, no. 1 (1996): 91-102. Wear, Martin A., Dorothy A. Schafer, and John A. Cooper. "Actin dynamics: assembly and disassembly of actin networks." Current Biology 10, no. 24 (2000): R891-R895. Peters, Alan, and Sanford L. Palay. "The morphology of synapses." Journal of neurocytology 25, no. 1 (1996): 687-700. Wilson, C. J., P. M. Groves, S. T. Kitai, and J. C. Linder. "Three-dimensional structure of dendritic spines in the rat neostriatum." The Journal of Neuroscience 3, no. 2 (1983): 383-388. Keywords: AMPA receptor trafficking, PSD-95, Bdnf-trkB signaling, Morphogenesis, actin polymerization, neurotransmitters Conference: Neuroinformatics 2014, Leiden, Netherlands, 25 Aug - 27 Aug, 2014. Presentation Type: Poster, not to be considered for oral presentation Topic: Computational neuroscience Citation: Nagarajan V, Raghu V, Chandrasekar G and Mallampalli K (2014). Growth and development of the postsynaptic active region of an excitatory glutemergic synapse: An integrated model. Front. Neuroinform. Conference Abstract: Neuroinformatics 2014. doi: 10.3389/conf.fninf.2014.18.00056 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 22 Apr 2014; Published Online: 04 Jun 2014. * Correspondence: Prof. Venkateswaran Nagarajan, Waran Research Foundation, Chennai, Tamil Nadu, 600033, India, waran@warftindia.org Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Venkateswaran Nagarajan Vishal Raghu Ganesh Ranganath Chandrasekar Kapardi Mallampalli Google Venkateswaran Nagarajan Vishal Raghu Ganesh Ranganath Chandrasekar Kapardi Mallampalli Google Scholar Venkateswaran Nagarajan Vishal Raghu Ganesh Ranganath Chandrasekar Kapardi Mallampalli PubMed Venkateswaran Nagarajan Vishal Raghu Ganesh Ranganath Chandrasekar Kapardi Mallampalli Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Size and position matter

The 2013 Nobel Prize in Physiology or Medicine emphasizes the progress made in understanding the molecular mechanisms that underpin the vesicular movement of cargo through the exocytic and endocytic pathways. Attention now focuses on those mechanisms that govern the relative size and position of the many different membrane-bound compartments. These homeostatic mechanisms are discussed in this issue of Nature Reviews Molecular Cell Biology and must be integrated so as to satisfy the needs of the cell and the organism.

Telling right from wrong in life — cellular quality control

An astounding ability to discriminate functional molecules from a range of unsuitable molecules is the cornerstone of cellular physiology. In all living cells, a hierarchy of communicating mechanisms directed at identifying, isolating, removing or repairing damaged molecules continuously monitors and maintains genomic integrity and cellular homeostasis, ensuring survival under changing and adverse conditions. This network interconnects with cytoprotective processes, which act preventively to avoid damage before it occurs. Altogether, this represents a massive evolutionary investment in cellular quality control. Four articles in this issue of Nature Reviews Molecular Cell Biology offer insights into emerging aspects of the cellular quality control network relating to RNA and proteins.

Erratum: Macrodomain-containing proteins: regulating new intracellular functions of mono(ADP-ribosyl)ation

Nature Reviews Molecular Cell Biology 14, 445–453 (2013) On page 443 of this article, the incorrect references were cited at the end of the following sentence: “Four years ago, macrodomains were shown to be able to bind PAR that has been synthesized in response to DNA damage18–20.” The authors meantto refer to references 20, 25 and 26 at the end of this sentence.

Erratum: Alternative splicing: a pivotal step between eukaryotic transcription and translation

Nature Reviews Molecular Cell Biology 14, 153–165 (2013) In the above article, the sentence on page 156 should have read: "A minority of budding yeast genes have a single long intron and, interestingly, pausing of Pol II is more abundant in genes that contain short exons than in those containing long exons.