Complex Signal Transduction Research Articles

Position-dependent roles of somatic cells in phototaxis of Volvox

Abstract A spherical green alga, Volvox, achieves phototaxis via a simple on/off switch of flagellar beating in response to changes in light intensity, without the need for complex signal transduction between cells. Moreover, the alga can change its susceptibility to light in order to adapt to its environment. To identify the mechanisms of susceptibility regulation, experiments were conducted at three different levels: population, individual, and cellular. The light intensity dependence of the average velocity at the population level and that of the change in flow speed obtained at the individual level were consistent, indicating that susceptibility regulation occurred in each Volvox colony. Furthermore, by measuring the probability of stopping flagellar beating when the light intensity was changed, susceptibility regulation was found to result from the properties of somatic cells as differential and adaptive photosensors. These photosensing properties deteriorated from the anterior to the posterior regions of the colony. Considering the mechanical motion of a Volvox colony, the position-dependent ability of somatic cells indicates that the anterior cells play the role of a rudder, whereas the posterior cells play the role of a rower. The position-dependent properties of somatic cells imply an early stage of cell differentiation that allows for an efficient response to changes in the circumstances.

Copper (II)-catalyzed polydopamine mediated photothermal sensors for visual quantitative point-of-care testing

BackgroundTemperature sensing is commonly used in point-of-care (POC) detection technologies, yet the portability and convenience of use are frequently compromised by the complexity of thermosensitive processes and signal transduction. Especially, multi-step target recognition reactions and temperature measurement in the reaction vessel present challenges in terms of stability and integration of detection devices. To further combine photothermal reaction and signal readout in one assay, these two processes enable to be integrated into miniaturized microfluidic chips, thereby facilitating photothermal sensing and achieving a simple visual temperature sensing as POC detection. ResultsA copper ion (Cu2+)-catalyzed photothermal sensing system integrated onto a microfluidic distance-based analytical device (μDAD), enabling the visual, portable, and sensitive quantitative detection of multiple targets, including ascorbic acid, glutathione, and alkaline phosphatase (ALP). The polydopamine nanoparticles (PDA NPs) were synthesized by the regulation of free Cu2+ through redox or coordination reactions, facilitating the transduction of distinct photothermal response signals and providing the versatile Cu2+-responsive sensing systems. Promoted by integration with a photothermal μDAD, the system combines PDA's photothermal responsiveness and thermosensitive gas production of ammonium bicarbonate for improved sensitivity of ALP detection, reaching the detection limit of 9.1 mU/L. The system has successfully achieved on-chip detection of ALP with superior anti-interference capability and recoveries ranging from 96.8 % to 104.7 %, alongside relative standard deviations below 8.0 %. Significance and noveltyThe μDAD design accommodated both the photothermal reaction of PDA NPs and thermosensitive gas production reaction, achieving the rapid sensing of visual distance signals. The μDAD-based Cu2+-catalyzed photothermal sensing system holds substantial potential for applications in biochemical analysis and clinical diagnostics, underscored by the versatile Cu2+ regulation mechanism for a broad spectrum of biomarkers.

Influence of expression and purification protocols on Gα biochemical activity: kinetics of plant and mammalian G protein cycles.

Heterotrimeric G proteins are a class of signal transduction complexes with broad roles in human health and agriculturally important plant traits. In the classic paradigm, guanine nucleotide binding to the Gα subunit regulates the activation status of the complex. Using the Arabidopsis thaliana Gα subunit, GPA1, we developed a rapid StrepII-tag mediated purification method that facilitates isolation of protein with increased enzymatic activities as compared to conventional methods, and is demonstrably also applicable to mammalian Gα subunits. We subsequently utilized domain swaps of GPA1 and human GNAO1 to demonstrate the instability of recombinant GPA1 is a function of the interaction between the Ras and helical domains, and can be partially uncoupled from the rapid nucleotide binding kinetics displayed by GPA1.

A Zero-Voltage-Writing Artificial Nervous System Based on Biosensor Integrated on Ferroelectric Tunnel Junction.

The artificial nervous system proves the great potential for the emulation of complex neural signal transduction. However, a more bionic system design for bio-signal transduction still lags behind that of physical signals, and relies on additional external sources. Here, this work presents a zero-voltage-writing artificial nervous system (ZANS) that integrates a bio-source-sensing device (BSSD) for ion-based sensing and power generation with a hafnium-zirconium oxide-ferroelectric tunnel junction (HZO-FTJ) for the continuously adjustable resistance state. The BSSD can use ion bio-source as both perception and energy source, and then output voltage signals varied with the change of ion concentrations to the HZO-FTJ, which completes the zero-voltage-writing neuromorphic bio-signal modulation. In view of in/ex vivo biocompatibility, this work shows the precise muscle control of a rabbit leg by integrating the ZANS with a flexible nerve stimulation electrode. The independence on external source enhances the application potential of ZANS in robotics and prosthetics.

TSPYL1 as a Critical Regulator of TGFβ Signaling through Repression of TGFBR1 and TSPYL2.

Nucleosome assembly proteins (NAPs) have been identified as histone chaperons. Testis-Specific Protein, Y-Encoded-Like (TSPYL) is a newly arisen NAP family in mammals. TSPYL2 can be transcriptionally induced by DNA damage and TGFβ causing proliferation arrest. TSPYL1, another TSPYL family member, has been poorly characterized and is the only TSPYL family member known to be causal of a lethal recessive disease in humans. This study shows that TSPYL1 and TSPYL2 play an opposite role in TGFβ signaling. TSPYL1 partners with the transcription factor FOXA1 and histone methyltransferase EZH2, and at the same time represses TGFBR1 and epithelial-mesenchymal transition (EMT). Depletion of TSPYL1 increases TGFBR1 expression, upregulates TGFβ signaling, and elevates the protein stability of TSPYL2. Intriguingly, TSPYL2 forms part of the SMAD2/3/4 signal transduction complex upon stimulation by TGFβ to execute the transcriptional responses. Depletion of TSPYL2 rescues the EMT phenotype of TSPYL1 knockdown in A549 lung carcinoma cells. The data demonstrates the prime role of TSPYL2 in causing the dramatic defects in TSPYL1 deficiency. An intricate counter-balancing role of TSPYL1 and TSPYL2 in regulating TGFβ signaling is also unraveled.

Use of interactive mathematical simulations in Fundamentals of Biochemistry, a LibreText online educational resource, to promote understanding of dynamic reactions.

Biology is perhaps the most complex of the sciences, given the incredible variety of chemical species that are interconnected in spatial and temporal pathways that are daunting to understand. Their interconnections lead to emergent properties such as memory, consciousness, and recognition of self and non-self. To understand how these interconnected reactions lead to cellular life characterized by activation, inhibition, regulation, homeostasis, and adaptation, computational analyses and simulations are essential, a fact recognized by the biological communities. At the same time, students struggle to understand and apply binding and kinetic analyses for the simplest reactions such as the irreversible first-order conversion of a single reactant to a product. This likely results from cognitive difficulties in combining structural, chemical, mathematical, and textual descriptions of binding and catalytic reactions. To help students better understand dynamic reactions and their analyses, we have introduced two kinds of interactive graphs and simulations into the online educational resource, Fundamentals of Biochemistry, a LibreText biochemistry book. One is available for simple binding and kinetic reactions. The other displays progress curves (concentrations vs. time) for simple reactions and complex metabolic and signal transduction pathways. Users can move sliders to change dissociation and kinetic constants as well as initial concentrations and see instantaneous changes in the graphs. They can also export data into a spreadsheet for further processing, such as producing derivative Lineweaver-Burk and traditional Michaelis-Menten graphs of initial velocity (v0) versus substrate concentration.

Investigating the activity of Quinazoline derivatives against T790 mutant EGFR receptors employing computer-aided drug design

The uncontrolled growth of cancer cells is caused by their innate tendency to multiply without limits. In addition to colonizing adjacent tissues, they are capable of forming aggregates in isolated anatomical sites, thereby significantly increasing their invasiveness. Over time, malignant tumors that progressively destroy essential tissues and organs are ultimately lethal. It is well known that growth factor-driven signaling influence malignancy. The transmembrane receptor tyrosine kinases of growth factors influence the survival, differentiation, and proliferation of cells. To expedite cell division, neurotransmitters and proteins resembling epidermal growth factor (EGF) stimulate EGF receptor (EGFR) family members including HER2-4 and EGFR. The development and growth of numerous varieties of human cancer cells, as well as the morphogenesis of numerous animal species (nematodes to humans), are influenced by this signaling module, which is remarkably conserved. The EGFR family, consisting of over thirty ligands and four receptors, forms a complex and advanced human signal transduction network. The T790M mutation in the EGFR kinase enhances treatment resistance by increasing the affinity for ATP. This work used a molecular design tool to evaluate quinazoline derivatives with the highest IC50 values against EGFR and analyze the molecular interactions in the binding site. The goal was to uncover novel compounds with promising potential.

Genome-Wide Identification and Expression Analysis Reveals the B3 Superfamily Involved in Embryogenesis and Hormone Responses in Dimocarpus longan Lour.

B3 family transcription factors play an essential regulatory role in plant growth and development processes. This study performed a comprehensive analysis of the B3 family transcription factor in longan (Dimocarpus longan Lour.), and a total of 75 DlB3 genes were identified. DlB3 genes were unevenly distributed on the 15 chromosomes of longan. Based on the protein domain similarities and functional diversities, the DlB3 family was further clustered into four subgroups (ARF, RAV, LAV, and REM). Bioinformatics and comparative analyses of B3 superfamily expression were conducted in different light and with different temperatures and tissues, and early somatic embryogenesis (SE) revealed its specific expression profile and potential biological functions during longan early SE. The qRT-PCR results indicated that DlB3 family members played a crucial role in longan SE and zygotic embryo development. Exogenous treatments of 2,4-D (2,4-dichlorophenoxyacetic acid), NPA (N-1-naphthylphthalamic acid), and PP333 (paclobutrazol) could significantly inhibit the expression of the DlB3 family. Supplementary ABA (abscisic acid), IAA (indole-3-acetic acid), and GA3 (gibberellin) suppressed the expressions of DlLEC2, DlARF16, DlTEM1, DlVAL2, and DlREM40, but DlFUS3, DlARF5, and DlREM9 showed an opposite trend. Furthermore, subcellular localization indicated that DlLEC2 and DlFUS3 were located in the nucleus, suggesting that they played a role in the nucleus. Therefore, DlB3s might be involved in complex plant hormone signal transduction pathways during longan SE and zygotic embryo development.

Genetic and molecular landscapes of the generalist phytopathogen Botrytis cinerea.

Kingdom: Fungi, phylum: Ascomycota, subphylum: Pezizomycotina, class: Leotiomycetes, order: Helotiales, family: Sclerotiniaceae, genus: Botrytis, species: cinerea. B. cinerea infects almost all of the plant groups (angiosperms, gymnosperms, pteridophytes, and bryophytes). To date, 1606 plant species have been identified as hosts of B. cinerea. This polyphagous necrotroph has extensive genetic diversity at all population levels shaped by climate, geography, and plant host variation. Genetic architecture of virulence and host specificity is polygenic using multiple weapons to target hosts, including secretory proteins, complex signal transduction pathways, metabolites, and mobile small RNA. Efforts to control B. cinerea, being a high-diversity generalist pathogen, are complicated. However, integrated disease management strategies that combine cultural practices, chemical and biological controls, and the use of appropriate crop varieties will lessen yield losses. Recently, studies conducted worldwide have explored the potential of small RNA as an efficient and environmentally friendly approach for combating grey mould. However, additional research is necessary, especially on risk assessment and regulatory frameworks, to fully harness the potential of this technology.

Abstract 17551: Mapping the Interactome of FLNC in Restrictive Cardiomyopathy

Introduction: Filamin C (FLNC) is an actin crosslinking protein that organizes structural components of the sarcomere and signal transduction complexes. Human mutations in FLNC have been linked to dilated, hypertrophic and restrictive cardiomyopathies. The mechanism connecting mutations in FLNC to sarcomeric impairment remains undefined. We recently reported the ability to model FLNC cardiomyopathy using induced pluripotent stem cell (iPSC) derived engineered heart tissue. Here, we employ a knock-in approach to epitope tag endogenous alleles in iPSC derived cardiomyocytes to explore FLNC genotype-interactome relationships using affinity purification mass spectrometry. Methods: An iPSC line was generated from a patient with restrictive cardiomyopathy caused by an insertion deletion mutation in the ROD2 domain FLNC (c.7416_7418delGAA, p.Glu2472_Asn2473delinAsp). CRISPR-Cas9 was used to establish a corrected cell line as a wild type control. 3X-Flag motif was introduced to the N terminus of FLNC using CRISPR-Cas9. iPSCs were then differentiated into cardiomyocytes using standard techniques. Affinity purification mass spectrometry (AP-MS) was performed using the Flag epitope. Interaction data was analyzed using Perseus software. Gene ontology (GO) enrichment analysis was performed using ToppFun. Results: 3X-Flag insertion was confirmed using genomic sequencing. AP-MS identified 281 high confidence interactors of mutant FLNC and 208 interactors of wild type FLNC (FDR 0.01, log2FC >1.5) when compared to IgG controls. Interestingly, 161 proteins were shared between the two genotypes. These were enriched in mitochondrial ribosomal proteins and phosphorylase kinase subunits, potentially revealing an unknown role of FLNC in mitochondria translation and metabolism. Thirty-three proteins were significantly differentially bound to mutant FLNC protein, including tropomyosin 4, caldesmon 1, and filamin A (FDR <0.05, log2FC>1). GO analysis of these proteins revealed enrichment of actin cytoskeleton elements, muscle contraction, and muscle system processes. Conclusions: Human mutations in FLNC lead to disruption of key protein interactions, revealing a potential mechanism for disease pathogenesis in FLNC cardiomyopathy.

PDZ scaffolds regulate extracellular vesicle production, composition, and uptake

Extracellular vesicles (EVs) are membrane-limited organelles mediating cell-to-cell communication in health and disease. EVs are of high medical interest, but their rational use for diagnostics or therapies is restricted by our limited understanding of the molecular mechanisms governing EV biology. Here, we tested whether PDZ proteins, molecular scaffolds that support the formation, transport, and function of signal transduction complexes and that coevolved with multicellularity, may represent important EV regulators. We reveal that the PDZ proteome (ca. 150 proteins in human) establishes a discrete number of direct interactions with the tetraspanins CD9, CD63, and CD81, well-known EV constituents. Strikingly, PDZ proteins interact more extensively with syndecans (SDCs), ubiquitous membrane proteins for which we previously demonstrated an important role in EV biogenesis, loading, and turnover. Nine PDZ proteins were tested in loss-of-function studies. We document that these PDZ proteins regulate both tetraspanins and SDCs, differentially affecting their steady-state levels, subcellular localizations, metabolism, endosomal budding, and accumulations in EVs. Importantly, we also show that PDZ proteins control the levels of heparan sulfate at the cell surface that functions in EV capture. In conclusion, our study establishes that the extensive networking of SDCs, tetraspanins, and PDZ proteins contributes to EV heterogeneity and turnover, highlighting an important piece of the molecular framework governing intracellular trafficking and intercellular communication.

Bifunctional near-infrared fluorescent probe for the selective detection of bisulfite and hypochlorous acid in food, water samples and in vivo

We report the development of a bifunctional near-infrared fluorescent probe (QZB) for selective sensing of bisulfite (HSO3−) and hypochlorous acid (HOCl). The synergistic detection of HSO3− and HOCl was achieved via a C=C bond recognition site. In comparison with the red-fluorescence QZB, two different products with non-fluorescence and paleturquoise fluorescence were produced by the recognition of QZB towards HSO3− and HOCl respectively, which can realize effectively the dual-functional detection of HSO3− and HOCl. QZB features prominent preponderances of dual-function response, near-infrared emission, reliability at physiological pH, low cytotoxicity and high sensitivity to HSO3− and HOCl. The detection of HSO3− in actual food samples has been successfully achieved using QZB. Utilization of QZB-based test strip to semi-quantitatively detect HSO3− and HOCl in real-world water samples by the “naked-eye” colorimetry are then demonstrated. Simultaneously, the determination of HSO3− and HOCl in real-world water sample has been achieved by smartphone-based standard curves. Additionally, the applications of QZB for imaging HSO3− and HOCl in vivo are successfully demonstrated. Consequently, the successful development of QZB could be promising as an efficient tool for researching the role of HSO3−/HOCl in the regulation of redox homeostasis regulation in vivo and complex signal transduction and for future food safety evaluation.

(Invited) Multimodality Sensing and Actuation Using Nanocarbons

My team’s efforts are focused on the development and engineering of nanocarbons-based flexible platforms to interrogate and affect the properties of cells and tissue, with a specific goal to understand signal transduction (chemical or electrical) in tissue or complex 3D cellular assemblies. Our highly flexible bottom-up nanomaterials synthesis capabilities allow us to form unique hybrid-nanomaterials that can be used in various input/output bioelectrical interfaces, i.e., bioelectrical platforms for chemical and physical sensing and actuation. We have developed several approaches for monitoring (and affecting) the complex signal transduction in 3D cellular assemblies toward an organ-on-an-electronic-chip (organ-on-e-chip) platform for tissue maturation and disease progression investigations. Utilizing graphene, a two-dimensional (2D) atomically thin carbon allotrope, we can simultaneously record the intracellular electrical activity of multiple excitable cells with ultra-microelectrodes that can be as small as an axon (ca. 2µm). The outstanding electrochemical properties of the synthesized hybrid-nanomaterials allow us to develop highly efficient catalysts, that can be deployed as electrical sensors and (chemical) actuators. We demonstrated sensors capable of exploring brain chemistry and sensors/actuators that are deployed in a large volumetric muscle loss animal model. Finally, using the unique optical properties of nanocarbons in the form of graphene-based hybrid-nanomaterials and 2D nanocarbides (MXene), we have formed remote, non-genetic bioelectrical interfaces with excitable cells and modulated cellular and network activity with low needed energy and high precision. In summary, the exceptional synthetic control and flexible assembly of nanomaterials provide powerful tools for fundamental studies and applications in life science and potentially seamlessly merge nanomaterials-based platforms with cells, fusing nonliving and living systems together.

Expression variations of DNA damage response genes ATM and ATR in blood cancer patients.

Hematological malignancies (HM) constitute a variety of cancers originating in blood, bone marrow (BM), and lymphatic systems. During the last two decades, the incidence of HM has dramatically increased worldwide. The etiology of HM is still debatable. Genetic instability is a major risk factor for HM. DDR network is a complex signal transduction cellular machinery that detects DNA damage and activates cellular repair factors, thus maintaining genomic integrity. DDR network detects a variety of DNA damage and triggers the activation of cell cycle control, DNA repair, senescence, and apoptosis. Among the DNA repairing pathways, the DNA damage response (DDR) pathway includes DNA damage signaling apparatus such as ATM and ATR genes. ATM tends to detect double-strand breaks (DSBs) while ATR detects single-strand DNA (ssDNA). The study was conducted to observe the expression deregulations of DNA damage response (DDR) pathway genes (ATM, ATR) at mRNA level in 200 blood cancer patients and 200 controls. The real-time PCR was used to analyze the expression of the target genes. The expression results showed statistically significant downregulation of ATM (p < 0.0001) and ATR (p < 0.0001) genes in blood cancer patients vs. controls. Moreover, a significant downregulation of ATM (p < 0.0001) and ATR (p < 0.0001) was obtained in chemotherapy-treated patients vs. healthy controls. The results suggest that dysregulation in ATM and ATR genes may be associated with increased blood cancer risk.

CNK2 promotes cancer cell motility by mediating ARF6 activation downstream of AXL signalling

Cell motility is a critical feature of invasive tumour cells that is governed by complex signal transduction events. Particularly, the underlying mechanisms that bridge extracellular stimuli to the molecular machinery driving motility remain partially understood. Here, we show that the scaffold protein CNK2 promotes cancer cell migration by coupling the pro-metastatic receptor tyrosine kinase AXL to downstream activation of ARF6 GTPase. Mechanistically, AXL signalling induces PI3K-dependent recruitment of CNK2 to the plasma membrane. In turn, CNK2 stimulates ARF6 by associating with cytohesin ARF GEFs and with a novel adaptor protein called SAMD12. ARF6-GTP then controls motile forces by coordinating the respective activation and inhibition of RAC1 and RHOA GTPases. Significantly, genetic ablation of CNK2 or SAMD12 reduces metastasis in a mouse xenograft model. Together, this work identifies CNK2 and its partner SAMD12 as key components of a novel pro-motility pathway in cancer cells, which could be targeted in metastasis.

Progesterone signaling in regulation of luteal steroidogenesis.

The corpus luteum is the major source of progesterone, the essential hormone for female reproductive function. While progesterone activity has been the subject of extensive research for decades, characterization of noncanonical progesterone receptor/signaling pathways provided a new perspective for understanding the complex signal transduction mechanisms exploited by the progesterone hormone. Deciphering these mechanisms has significant implications in the management of luteal phase disorders and early pregnancy complications. The purpose of this review is to highlight the complex mechanisms through which progesterone-induced signaling mediates luteal granulosa cell activity in the corpus luteum. Here we review the literature and discuss the up-to-date evidence on how paracrine and autocrine effects of progesterone regulate luteal steroidogenic activity. We also review the limitations of the published data and highlight future research priorities.

L-Ascorbic acid metabolism and regulation in fruit crops.

L-Ascorbic acid (AsA) is more commonly known as vitamin C and is an indispensable compound for human health. As a major antioxidant, AsA not only maintains redox balance and resists biological and abiotic stress but also regulates plant growth, induces flowering, and delays senescence through complex signal transduction networks. However, AsA content varies greatly in horticultural crops, especially in fruit crops. The AsA content of the highest species is approximately 1,800 times higher than that of the lowest species. There have been significant advancements in the understanding of AsA accumulation in the past 20 years. The most noteworthy accomplishment was the identification of the critical rate-limiting genes for the 2 major AsA synthesis pathways (L-galactose pathway and D-galacturonic acid pathway) in fruit crops. The rate-limiting genes of the former are GMP, GME, GGP, and GPP, and the rate-limiting gene of the latter is GalUR. Moreover, APX, MDHAR, and DHAR are also regarded as key genes in degradation and regeneration pathways. Interestingly, some of these key genes are sensitive to environmental factors, such as GGP being induced by light. The efficiency of enhancing AsA content is high by editing upstream open reading frames (uORF) of the key genes and constructing multi-gene expression vectors. In summary, the AsA metabolism has been well understood in fruit crops, but the transport mechanism of AsA and the synergistic improvement of AsA and other traits is less known, which will be the focus of AsA research in fruit crops.

The roles of plant proteases and protease inhibitors in drought response: a review.

Upon exposure to drought, plants undergo complex signal transduction events with concomitant changes in the expression of genes, proteins and metabolites. For example, proteomics studies continue to identify multitudes of drought-responsive proteins with diverse roles in drought adaptation. Among these are protein degradation processes that activate enzymes and signalling peptides, recycle nitrogen sources, and maintain protein turnover and homeostasis under stressful environments. Here, we review the differential expression and functional activities of plant protease and protease inhibitor proteins under drought stress, mainly focusing on comparative studies involving genotypes of contrasting drought phenotypes. We further explore studies of transgenic plants either overexpressing or repressing proteases or their inhibitors under drought conditions and discuss the potential roles of these transgenes in drought response. Overall, the review highlights the integral role of protein degradation during plant survival under water deficits, irrespective of the genotypes' level of drought resilience. However, drought-sensitive genotypes exhibit higher proteolytic activities, while drought-tolerant genotypes tend to protect proteins from degradation by expressing more protease inhibitors. In addition, transgenic plant biology studies implicate proteases and protease inhibitors in various other physiological functions under drought stress. These include the regulation of stomatal closure, maintenance of relative water content, phytohormonal signalling systems including abscisic acid (ABA) signalling, and the induction of ABA-related stress genes, all of which are essential for maintaining cellular homeostasis under water deficits. Therefore, more validation studies are required to explore the various functions of proteases and their inhibitors under water limitation and their contributions towards drought adaptation.

How cells sense and integrate information from different sources.

Cell signaling is a fundamental cellular process that enables cells to sense and respond to information in their surroundings. At the molecular level, signaling is primarily carried out by transmembrane protein receptors that can initiate complex downstream signal transduction cascades to alter cellular behavior. In the human body, different cells can be exposed to a wide variety of environmental conditions, and cells express diverse classes of receptors capable of sensing and integrating different signals. Furthermore, different receptors and signaling pathways can crosstalk with each other to calibrate the cellular response. Crosstalk occurs through multiple mechanisms at different levels of signaling pathways. In this review, we discuss how cells sense and integrate different chemical, mechanical, and spatial signals as well as the mechanisms of crosstalk between pathways. To illustrate these concepts, we use a few well-studied signaling pathways, including receptor tyrosine kinases and integrin receptors. Finally, we discuss the implications of dysregulated cellular sensing on driving diseases such as cancer. This article is categorized under: Cancer > Molecular and Cellular Physiology Metabolic Diseases > Molecular and Cellular Physiology.

Сериновые протеазы в функциональной активности нервной системы

Serine proteases, including trypsin, thrombin, plasminogen activators, plasmin and several others, are synthesized in nervous tissue, mainly in the brain, including the cortex, limbic system and cerebellum. This review examines the involvement of serine proteases in neuroplasticity and behavioral regulation. Endogenous serine proteases play an important role in the formation, development and maintenance of the nervous system. Through limited proteolysis, these proteases activate PARs (protease-activated receptors), modify other receptors or their ligands, process neurotrophic factors, degrade intercellular matrix and cell adhesion proteins and initiate complex signal transduction cascades necessary for structural modification of synapses. The involvement of serine proteases in morphological and functional synaptic plasticity may underlie cognitive processes, including learning and memory in animals and humans.