Nomenclature For Proteins Research Articles

New insights into the functions of ACBD4/5-like proteins using a combined phylogenetic and experimental approach across model organisms

Acyl-CoA binding domain-containing proteins (ACBDs) perform diverse but often uncharacterised functions linked to cellular lipid metabolism. Human ACBD4 and ACBD5 are closely related peroxisomal membrane proteins, involved in tethering of peroxisomes to the ER and capturing fatty acids for peroxisomal β-oxidation. ACBD5 deficiency causes neurological abnormalities including ataxia and white matter disease. Peroxisome-ER contacts depend on an ACBD4/5-FFAT motif, which interacts with ER-resident VAP proteins. As ACBD4/5-like proteins are present in most fungi and all animals, we combined phylogenetic analyses with experimental approaches to improve understanding of their evolution and functions. Notably, all vertebrates exhibit gene sequences for both ACBD4 and ACBD5, while invertebrates and fungi possess only a single ACBD4/5-like protein. Our analyses revealed alterations in domain structure and FFAT sequences, which help understanding functional diversification of ACBD4/5-like proteins. We show that the Drosophila melanogaster ACBD4/5-like protein possesses a functional FFAT motif to tether peroxisomes to the ER via Dm_Vap33. Depletion of Dm_Acbd4/5 caused peroxisome redistribution in wing neurons and reduced life expectancy. In contrast, the ACBD4/5-like protein of the filamentous fungus Ustilago maydis lacks a FFAT motif and does not interact with Um_Vap33. Loss of Um_Acbd4/5 resulted in an accumulation of peroxisomes and early endosomes at the hyphal tip. Moreover, lipid droplet numbers increased, and mitochondrial membrane potential declined, implying altered lipid homeostasis. Our findings reveal differences between tethering and metabolic functions of ACBD4/5-like proteins across evolution, improving our understanding of ACBD4/5 function in health and disease. The need for a unifying nomenclature for ACBD proteins is discussed.

An approach for proteins and their encoding genes synonyms integration based on protein ontology

BackgroundBiological research is generating high volumes of data distributed across various sources. The inconsistent naming of proteins and their encoding genes brings great challenges to protein data integration: proteins and their coding genes usually have multiple related names and notations, which are difficult to match absolutely; the nomenclature of genes and proteins is complex and varies from species to species; some less studied species have no nomenclature of genes and proteins; The annotation of the same protein/gene varies greatly in different databases. In summary, a comprehensive set of protein/gene synonyms is necessary for relevant studies.ResultsIn this study, we propose an approach for protein and its encoding gene synonym integration based on protein ontology. The workflow of protein and gene synonym integration is composed of three modules: data acquisition, entity and attribute alignment, attribute integration and deduplication. Finally, the integrated synonym set of proteins and their coding genes contains over 128.59 million terminologies covering 560,275 proteins/genes and 13,781 species. As the semantic basis, the comprehensive synonym set was used to develop a data platform to provide one-stop data retrieval without considering the diversity of protein nomenclature and species.ConclusionThe synonym set constructed here can serve as an important resource for biological named entity identification, text mining and information retrieval without name ambiguity, especially synonyms associated with well-defined species categories can help to study the evolutionary relationships between species at the molecular level. More importantly, the comprehensive synonyms set is the semantic basis for our subsequent studies on Protein–protein Interaction (PPI) knowledge graph.

The Clinical Impact of Proteomics in Amyloid Typing

The Clinical Impact of Proteomics in Amyloid Typing

ATP binding cassette importers in eukaryotic organisms.

ATP-binding cassette (ABC) transporters are ubiquitous across all realms of life. Dogma suggests that bacterial ABC transporters include both importers and exporters, whilst eukaryotic members of this family are solely exporters, implying that ABC import function was lost during evolution. This view is being challenged, for example energy-coupling factor (ECF)-type ABC importers appear to fulfil important roles in both algae and plants where they form the ABCI sub-family. Herein we discuss whether bacterial Type I and Type II ABC importers also made the transition into extant eukaryotes. Various studies suggest that Type I importers exist in algae and the liverwort family of primitive non-vascular plants, but not in higher plants. The existence of eukaryotic Type II importers is also supported: a transmembrane protein homologous to vitamin B12 import system transmembrane protein (BtuC), hemin transport system transmembrane protein (HmuU) and high-affinity zinc uptake system membrane protein (ZnuB) is present in the Cyanophora paradoxa genome. This protein has homologs within the genomes of red algae. Furthermore, its candidate nucleotide-binding domain (NBD) shows closest similarity to other bacterial Type II importer NBDs such as BtuD. Functional studies suggest that Type I importers have roles in maintaining sulphate levels in the chloroplast, whilst Type II importers probably act as importers of Mn2+ or Zn2+ , as inferred by comparisons with bacterial homologs. Possible explanations for the presence of these transporters in simple plants, but not in other eukaryotic organisms, are considered. In order to utilise the existing nomenclature for eukaryotic ABC proteins, we propose that eukaryotic Type I and II importers be classified as ABCJ and ABCK transporters, respectively.

Standardizing gene product nomenclature—a call to action

The current lack of a standardized nomenclature system for gene products (e.g., proteins) has resulted in a haphazard counterproductive system of labeling. Different names are often used for the same gene product; the same name is sometimes used for unrelated gene products. Such ambiguity causes not only potential harm to patients, whose treatments increasingly rely on laboratory tests for multiple gene products, but also miscommunication and inefficiency, both of which hinder progress of broad scientific fields. To mitigate this confusion, we recommend standardizing human protein nomenclature through the use of a Human Genome Organisation (HUGO) Gene Nomenclature Committee (HGNC) gene symbol accompanied by its unique HGNC ID. We call for action across all biomedical communities and scientific and medical journals to standardize nomenclature of gene products using HGNC gene symbols to enhance accuracy in scientific and public communication. We call on all biomedical communities and scientific and medical journals to standardize nomenclature of gene products to enhance accuracy in scientific and public communication. Image credit: Shutterstock/greenbutterfly. Use of gene symbols designated by the HGNC [www.genenames.org (1)] is nearly universal. DNA- and RNA-level sequence variation nomenclature has been standardized to use HGNC gene symbols, the Single Nucleotide Polymorphism database (dbSNP) IDs, and genetic variant nomenclature designated by the Human Genome Variation Society (HGVS) to unambiguously designate variants. In striking contrast to the use of universal identifiers for genes and gene variants, there are no universal identifiers for the peptides and proteins that these genes encode. Many gene products have multiple nomenclatures in widespread use, and many common nomenclatures are used for multiple gene products. For example, the symbol “PD-1” is shared by multiple unrelated gene products and is used to describe PDCD1 , SNCA , and SPATA2 gene products. The PDCD1 (PD-1) protein is a well-known target for cancer immunotherapy. … [↵][1]1To whom correspondence may be addressed. Email: elspeth@ebi.ac.uk, timothy.oleary@va.gov, or sogino{at}bwh.harvard.edu. [1]: #xref-corresp-1-1

Role of GTPases in Driving Mitoribosome Assembly.

Mitoribosomes catalyze essential protein synthesis within mitochondria. Mitoribosome biogenesis is assisted by an increasing number of assembly factors, among which guanosine triphosphate hydrolases (GTPases) are the most abundant class. Here, we review recent progress in our understanding of mitoribosome assembly GTPases. We describe their shared and specific features and mechanisms of action, compare them with their bacterial counterparts, and discuss their possible roles in the assembly of small or large mitoribosomal subunits and the formation of the monosome by establishing quality-control checkpoints during these processes. Furthermore, following the recent unification of the nomenclature for the mitoribosomal proteins, we also propose a unified nomenclature for mitoribosome assembly GTPases.

Proteomics of Campylobacter jejuni Growth in Deoxycholate Reveals Cj0025c as a Cystine Transport Protein Required for Wild-type Human Infection Phenotypes

Campylobacter jejuni is a major cause of food-borne gastroenteritis. Proteomics by label-based two-dimensional liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) identified proteins associated with growth in 0.1% sodium deoxycholate (DOC, a component of gut bile salts), and system-wide validation was performed by data-independent acquisition (DIA-SWATH-MS). LC-MS/MS quantified 1326 proteins (∼82% of the predicted C. jejuni proteome), of which 1104 were validated in additional biological replicates by DIA-SWATH-MS. DOC resulted in a profound proteome shift with 512 proteins showing significantly altered abundance. Induced proteins were associated with flagellar motility and antibiotic resistance; and these correlated with increased DOC motility and resistance to polymyxin B and ciprofloxacin. DOC also increased human Caco-2 cell adherence and invasion. Abundances of proteins involved in nutrient transport were altered by DOC and aligned with intracellular changes to their respective carbon sources. DOC increased intracellular levels of sulfur-containing amino acids (cysteine and methionine) and the dipeptide cystine (Cys-Cys), which also correlated with reduced resistance to oxidative stress. A DOC induced transport protein was Cj0025c, which has sequence similarity to bacterial Cys-Cys transporters. Deletion of cj0025c (Δcj0025c) resulted in proteome changes consistent with sulfur starvation, as well as attenuated invasion, reduced motility, atypical morphology, increased antimicrobial susceptibility and poor biofilm formation. Targeted metabolomics showed Δcj0025c could use known C. jejuni amino and organic acid substrates commensurate with wild-type. Medium Cys-Cys levels however, were maintained in Δcj0025c relative to wild-type. A toxic Cys-Cys mimic (selenocystine) inhibited wild-type growth, but not Δcj0025c Provision of an alternate sulfur source (2 mm thiosulfate) restored Δcj0025c motility. Our data confirm that Cj0025c is a Cys-Cys transporter that we have named TcyP consistent with the nomenclature of homologous proteins in other species.

A structure-based nomenclature for Bacillus thuringiensis and other bacteria-derived pesticidal proteins

In 1998 a nomenclature for the growing list of pesticidal proteins from Bacillus thuringiensis (Bt) was derived based solely on protein sequence comparisons. This nomenclature was widely adopted and provided a robust framework for the naming and classification of the proteins. The success of these proteins in integrated pest management schemes prompted an increased effort to find others with improved or more diverse activities. These discovery activities led to the characterization of proteins from a wider range of bacteria and with a variety of different protein folds. Since most of these new proteins were grouped together as Cry proteins it became apparent that the existing nomenclature had limitations in representing the diverse range of proteins that had been identified. This revised nomenclature retains the basic principles of the 1998 version but provides specific mnemonics to represent different structural groups. For the purposes of consistency, the vast majority of the proteins have either retained their name or have a new name that clearly references the previous one. Other pesticidal proteins not previously included in the nomenclature have been incorporated into this version.

Comparative genomic analysis of eutherian connexin genes

The eutherian connexins were characterized as protein constituents of gap junctions implicated in cell-cell communications between adjoining cells in multiple cell types, regulation of major physiological processes and disease pathogeneses. However, conventional connexin gene and protein classifications could be regarded as unsuitable in descriptions of comprehensive eutherian connexin gene data sets, due to ambiguities and inconsistencies in connexin gene and protein nomenclatures. Using eutherian comparative genomic analysis protocol and 35 public eutherian reference genomic sequence data sets, the present analysis attempted to update and revise comprehensive eutherian connexin gene data sets, and address and resolve major discrepancies in their descriptions. Among 631 potential coding sequences, the tests of reliability of eutherian public genomic sequences annotated, in aggregate, 349 connexin complete coding sequences. The most comprehensive curated eutherian connexin gene data set described 21 major gene clusters, 4 of which included evidence of differential gene expansions. For example, the present gene annotations initially described human CXNK1 gene and annotated 22 human connexin genes. Phylogenetic tree calculations and calculations of pairwise nucleotide sequence identity patterns proposed revised and updated phylogenetic classification of eutherian connexin genes. Therefore, the present study integrating gene annotations, phylogenetic analysis and protein molecular evolution analysis proposed new nomenclature of eutherian connexin genes and proteins.

The haemoglobin subunits alpha and beta: Old and new genetic variants in the Italian Mediterranean buffalo

Haemoglobin (HB), the most widely distributed respiratory pigment in the animal kingdom, is among the best characterized oxygen-binding proteins, both at functional and molecular level. However, very little information is available about the genomic features of HB in river buffalo (Bubalus bubalis), even though there are reports in literature confirming the presence of interesting polymorphisms at the protein level in Mediterranean buffalo. We hence address the characterization of exonic as well as intronic nucleotide polymorphism in the haemoglobin subunit alpha and beta in a set of nine Italian Mediterranean buffaloes exhibiting different HB phenotypes. The nine buffaloes were selected from a random set of 398 samples, previously analysed for their HB protein polymorphism, in order to account for both globin variants and the evolution of intron variability within the most common domesticated species of the family Bovidae. All four sequenced clones of the subunit alpha were 1311 bp, whereas the length of the five different sequenced clones of the subunit beta ranged from 1841 to 1960 bp, due to an insertion of 119 nucleotides. Six polymorphic sites were detected in the four amplicons of alpha subunit. Among them, two variations concern exclusively haplotype A, while four sequence variations were found to be specific to haplotype B. Several variations, both in exonic and intronic regions, were detected in the B. bubalis subunit beta. In conclusion, the nucleotide sequence variants observed in this work substantiate the known haemoglobin protein polymorphisms, and an updated protein nomenclature is provided here. In addition, we observed a high sequence similarity in the overall pattern of variation in the haemoglobin subunits, possibly the results of a concerted evolution, with relatively more extensive gene homogenization in river buffalo than in other ruminant species.

Circular Permutation Obscures Universality of a Ribosomal Protein.

Functions, origins, and evolution of the translation system are best understood in the context of unambiguous and phylogenetically based taxonomy and nomenclature. Here, we map ribosomal proteins onto the tree of life and provide a nomenclature for ribosomal proteins that is consistent with phylogenetic relationships. We have increased the accuracy of homology relationships among ribosomal proteins, providing a more informative picture of their lineages. We demonstrate that bL33 (bacteria) and eL42 (archaea/eukarya) are homologs with common ancestry and acute similarities in sequence and structure. Their similarities were previously obscured by circular permutation. The most likely mechanism of permutation between bL33 and eL42 is duplication followed by fusion and deletion of both the first and last β-hairpins. bL33 and eL42 are composed of zinc ribbon protein folds, one of the most common zinc finger fold-groups of, and most frequently observed in translation-related domains. Bacterial-specific ribosomal protein bL33 and archaeal/eukaryotic-specific ribosomal protein eL42 are now both assigned the name of uL33, indicating a universal ribosomal protein. We provide a phylogenetic naming scheme for all ribosomal proteins that is based on phylogenetic relationships to be used as a tool for studying the systemics, evolution, and origins of the ribosome.

COMICS: Cartoon Visualization of Omics Data in Spatial Context Using Anatomical Ontologies.

COMICS is an interactive and open-access web platform for integration and visualization of molecular expression data in anatomograms of zebrafish, carp, and mouse model systems. Anatomical ontologies are used to map omics data across experiments and between an experiment and a particular visualization in a data-dependent manner. COMICS is built on top of several existing resources. Zebrafish and mouse anatomical ontologies with their controlled vocabulary (CV) and defined hierarchy are used with the ontoCAT R package to aggregate data for comparison and visualization. Libraries from the QGIS geographical information system are used with the R packages “maps” and “maptools” to visualize and interact with molecular expression data in anatomical drawings of the model systems. COMICS allows users to upload their own data from omics experiments, using any gene or protein nomenclature they wish, as long as CV terms are used to define anatomical regions or developmental stages. Common nomenclatures such as the ZFIN gene names and UniProt accessions are provided additional support. COMICS can be used to generate publication-quality visualizations of gene and protein expression across experiments. Unlike previous tools that have used anatomical ontologies to interpret imaging data in several animal models, including zebrafish, COMICS is designed to take spatially resolved data generated by dissection or fractionation and display this data in visually clear anatomical representations rather than large data tables. COMICS is optimized for ease-of-use, with a minimalistic web interface and automatic selection of the appropriate visual representation depending on the input data.

A novel chimeric Hepatitis B virus S/preS1 antigen produced in mammalian and plant cells elicits stronger humoral and cellular immune response than the standard vaccine-constituent, S protein

Chronic Hepatitis B Virus (HBV) infection leads to severe liver pathogenesis associated with significant morbidity and mortality. As no curable medication is yet available, vaccination remains the most cost-effective approach to limit HBV spreading and control the infection. Although safe and efficient, the standard vaccine based on production of the small (S) envelope protein in yeast fails to elicit an effective immune response in about 10% of vaccinated individuals, which are at risk of infection. One strategy to address this issue is the development of more immunogenic antigens. Here we describe a novel HBV antigen obtained by combining relevant immunogenic determinants of S and large (L) envelope proteins. Our approach was based on the insertion of residues 21-47 of the preS1 domain of the L protein (nomenclature according to genotype D), involved in virus attachment to hepatocytes, within the external antigenic loop of S. The resulting S/preS121-47 chimera was successfully produced in HEK293T and Nicotiana benthamiana plants, as a more economical recombinant protein production platform. Comparative biochemical, functional and electron microscopy analysis indicated assembly of the novel antigen into subviral particles in mammalian and plant cells. Importantly, these particles preserve both S- and preS1-specific epitopes and elicit significantly stronger humoral and cellular immune responses than the S protein, in both expression systems used. Our data promote this antigen as a promising vaccine candidate to overcome poor responsiveness to the conventional, S protein-based, HBV vaccine.

Phylogeny-Based Systematization of Arabidopsis Proteins with Histone H1 Globular Domain.

H1 (or linker) histones are basic nuclear proteins that possess an evolutionarily conserved nucleosome-binding globular domain, GH1. They perform critical functions in determining the accessibility of chromatin DNA to trans-acting factors. In most metazoan species studied so far, linker histones are highly heterogenous, with numerous nonallelic variants cooccurring in the same cells. The phylogenetic relationships among these variants as well as their structural and functional properties have been relatively well established. This contrasts markedly with the rather limited knowledge concerning the phylogeny and structural and functional roles of an unusually diverse group of GH1-containing proteins in plants. The dearth of information and the lack of a coherent phylogeny-based nomenclature of these proteins can lead to misunderstandings regarding their identity and possible relationships, thereby hampering plant chromatin research. Based on published data and our in silico and high-throughput analyses, we propose a systematization and coherent nomenclature of GH1-containing proteins of Arabidopsis (Arabidopsis thaliana [L.] Heynh) that will be useful for both the identification and structural and functional characterization of homologous proteins from other plant species.

Aquaporins in peripheral nociception

Aquaporins in peripheral nociception

Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines

The Nomenclature Committee of the International Society of Amyloidosis (ISA) met during the XVth Symposium of the Society, 3 July–7 July 2016, Uppsala, Sweden, to assess and formulate recommendations for nomenclature for amyloid fibril proteins and the clinical classification of the amyloidoses. An amyloid fibril must exhibit affinity for Congo red and with green, yellow or orange birefringence when the Congo red-stained deposits are viewed with polarized light. While congophilia and birefringence remain the gold standard for demonstration of amyloid deposits, new staining and imaging techniques are proving useful. To be included in the nomenclature list, in addition to congophilia and birefringence, the chemical identity of the protein must be unambiguously characterized by protein sequence analysis when possible. In general, it is insufficient to identify a mutation in the gene of a candidate amyloid protein without confirming the variant changes in the amyloid fibril protein. Each distinct form of amyloidosis is uniquely characterized by the chemical identity of the amyloid fibril protein that deposits in the extracellular spaces of tissues and organs and gives rise to the disease syndrome. The fibril proteins are designated as protein A followed by a suffix that is an abbreviation of the parent or precursor protein name. To date, there are 36 known extracellular fibril proteins in humans, 2 of which are iatrogenic in nature and 9 of which have also been identified in animals. Two newly recognized fibril proteins, AApoCII derived from apolipoprotein CII and AApoCIII derived from apolipoprotein CIII, have been added. AApoCII amyloidosis and AApoCIII amyloidosis are hereditary systemic amyloidoses. Intracellular protein inclusions displaying some of the properties of amyloid, “intracellular amyloid” have been reported. Two proteins which were previously characterized as intracellular inclusions, tau and α-synuclein, are now recognized to form extracellular deposits upon cell death and thus have been included in Table 1 as ATau and AαSyn.

Should wheat, barley, rye, and/or gluten be avoided in a 6-food elimination diet?

Eosinophilic esophagitis (EoE), a food antigen-mediated disease, is effectively treated with the dietary elimination of 6 foods commonly associated with food allergies (milk, wheat, egg, soy, tree nuts/peanuts, and fish/shellfish). Because wheat shares homologous proteins (including gluten) with barley and rye and can also be processed with these grains, some clinicians have suggested that barley and rye might also trigger EoE as a result of cross-reaction and/or cross-contamination with wheat. In this article, we discuss the theoretical risks of cross-reactivity and cross-contamination among wheat, barley, and rye proteins (including gluten); assess common practices at EoE treatment centers; and provide recommendations for dietary treatment and future studies of EoE.

A Novel β3 Intracytoplasmic Domain Mutation Associated with Macrothrombocytopenia: Structural Analysis in Comparison with Previously Reported Cases

Background: Glanzmann thrombasthenia (GT) is a moderate to severe inherited bleeding syndrome associating a lack of platelet aggregation with quantitative or qualitative deficiencies of the αIIbβ3 integrin. Rare patients with mutations in ITGA2B or ITGB3 genes show a variable GT-like phenotype associated with macrothrombocytopenia (MTP). Gain-of-function mutations that localize to the integrin cytoplasmic domains cause autosomal dominant MTP. We now report a novel heterozygous ΔLeu in ITGB3 causing a structural modification of the cytoplasmic domain of β3 in a family with moderate MTP. In silico modeling was performed to obtain structural insights into this and other known mutations affecting cytoplasmic domains of αIIb and β3 and impacting megakaryopoiesis.Aim: To help define structural changes in αIIbβ3 linked to MTP.Results: A novel in-frame heterozygous 3bp deletion (c.2230_2232delCTC) was identified by exome sequencing performed as part of the BRIDGE-BPD consortium project in a French pedigree with lifelong mucocutaneous bleeding. The consequence is the loss of β3 Leu718 (ΔL718) the second L of a LLITIHD motif of the mature protein (nomenclature used throughout). Platelets of the proband have (i) moderate expression of αIIbβ3, (ii) a major reduction in fibrinogen (Fg) and PAC-1 binding after ADP stimulation yet (iii) spontaneous Fg or PAC-1 binding to platelets was not seen. Western blotting showed a slightly slower migration of β3 and normal αIIb. The proband had a moderate MTP with platelet size heterogeneity and frequent enlarged α-granules regrouping several of normal size with Fg bound to the membrane of the α-granules as revealed by immunogold staining and electron microscopy. Platelet aggregation was much reduced with all physiologic agonists including TRAP with a reduced surface expression of P-selectin and diminished secretion. The same 3bp del in ITGB3 co-segregates with the platelet phenotype and bleeding across 3 generations in the family. We then performed molecular modeling (PyMol Molecular Graphics System version 1.3) to compare the structural effects of this mutation on αIIbβ3 with other cytoplasmic tail mutations described in the literature giving GT-like phenotypes and/or MTP. Firstly αIIb-R995Q/W or β3-D723H were confirmed to disrupt a salt bridge between the integrin subunits and induce the separation of their tails. PyMol modeling showed that the DL718 results in D723 being no longer in phase with R995 thereby disrupting the salt bridge. Significantly, introduction of a β-turn by an activating β3 L718P substitution again results in the spontaneous separation of the tails, once more through a conformational change of the mutated β3. In contrast, a previously reported ITGB3 C2268T variant resulting in Arg724*, a truncation coming after the deletion in our patient, or a β3 S752P substitution that completely blocks platelet aggregation and PAC-1 binding (and specific loss of kindlin-3 binding) despite a capacity to secrete a storage pool of Fg bound α-granule αIIbβ3 failed to give MTP despite resulting in a GT-like syndrome.Conclusions: The novel ITGB3 ΔL718 of β3 showed an intermediate phenotype with MTP, a much decreased platelet aggregation, a reduced activity of αIIbβ3 at the platelet surface but a progressive fusion of α-granules. This is despite the theoretical retention of the talin and kindlin-3 binding sites suggesting that transmembrane signaling is the principle defect. Our studies highlight how considerable phenotypic heterogeneity exists in patients with genetic variants affecting αIIb and β3 cytoplasmic domains and suggest different signaling mechanisms for surface and intracellular αIIbβ3 pools.*PN and ET; WHO and ATN made equal contributions,On behalf of the BRIDGE-Bleeding and Platelet Disorder Consortium DisclosuresNo relevant conflicts of interest to declare.

Ovarian Steroids Influence Cerebral Glucose Transporter Expression in a Region‐ and Isoform‐Specific Pattern

Cerebral glucose uptake is mediated by several members of the family of facilitated glucose transporters (protein nomenclature GLUT; gene nomenclature solute carrier family 2 Slc2a). Glucose uptake differs between the sexes and also varies with menstrual status in women and across the rodent oestrous cycle. The present study demonstrates the extent to which hormonal variation across the four stages of the rat oestrous cycle affects the mRNA abundance of four members of the GLUT family, including the most well characterised cerebral transporters Slc2a1 and Slc2a3, as well as the insulin-sensitive transporters Slc2a4 and Slc2a8 in the hypothalamus, hippocampus and prefrontal cortex. Slc2a1 varied significantly across the cycle in the hippocampus and prefrontal cortex, and Slc2a3 and Slc2a4 also showed significant fluctuation in the hippocampus. Transporter expression significantly increased during pro-oestrus in both the hippocampus and prefrontal cortex. Furthermore, ovarian hormones are critical for normal expression of GLUT mRNA, as demonstrated by reduced expression of Slc2a1, Slc2a3 and Sl2a8 in the hippocampus after ovariectomy. Collectively, the data reported in the present study demonstrate that glucose transporters are highly sensitive to hormonal variation and that this sensitivity is regionally distinct; thereby fluctuations likely have specific phenotypic implications.

High-Resolution Structure of the Eukaryotic 80S Ribosome

The high-resolution structure of the eukaryotic ribosome from yeast, determined at 3.0-Å resolution, permitted the unambiguous determination of the protein side chains, eukaryote-specific proteins, protein insertions, and ribosomal RNA expansion segments of the 80 proteins and ∼5,500 RNA bases that constitute the 80S ribosome. A comparison between this first atomic model of the entire 80S eukaryotic ribosome and previously determined structures of bacterial ribosomes confirmed early genetic and structural data indicating that they share an evolutionarily conserved core of ribosomal RNA and proteins. It also confirmed the conserved organization of essential functional sites, such as the peptidyl transferase center and the decoding site. New structural information about eukaryote-specific elements, such as expansion segments and new ribosomal proteins, forms the structural framework for the design and analysis of experiments that will explore the eukaryotic translational apparatus and the evolutionary forces that shaped it. New nomenclature for ribosomal proteins, based on the names of protein families, has been proposed.