81,301 results match your criteria gtp binding

RAB33B and PCNT variants in two Pakistani families with skeletal dysplasia and short stature.

BMC Musculoskelet Disord 2021 Jul 20;22(1):630. Epub 2021 Jul 20.

Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.

Background: Skeletal dysplasia is a heterogeneous group of disorders resulting from different genetic variants in humans. The current study was designed to identify the genetic causes of skeletal dysplasia and short stature in two consanguineous families from Pakistan, both comprised of multiple affected individuals. Patients in one family had proportionate short stature with reduced head circumference while affected individuals in the other family had disproportionate short stature. Read More

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Over-activation of EFTUD2 correlates with tumor propagation and poor survival outcomes in hepatocellular carcinoma.

Clin Transl Oncol 2021 Jul 19. Epub 2021 Jul 19.

Department of Gastroenterology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Rd, Shanghai, 201203, China.

Purpose: Elongation factor Tu GTP-binding domain containing 2 (EFTUD2) is an essential constituent of U5 small nuclear ribonucleoproteins (snRNPs) and plays a crucial role in spliceosome activation and cancer. The mechanism of EFTUD2 on carcinogenesis and development of liver cancer still need further study.

Methods: Bioinformatic analysis was performed to find differential expressed genes and related pathways. Read More

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Novel 61-bp Indel of Is Associated With Fat and Hatching Weight Traits in Chickens.

Front Genet 2021 1;12:672888. Epub 2021 Jul 1.

Department of Animal Genetics, Breeding, and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, China.

The Ras and Rab interactor 2 () gene, which encodes RAS and Rab interacting protein 2, can interact with GTP-bound Rab5 and participate in early endocytosis. This study found a 61-bp insertion/deletion (indel) in the intron region, and 3 genotypes , , and were observed. Genotype analysis of mutation sites was performed on 665 individuals from F population and 8 chicken breeds. Read More

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CTP regulates membrane-binding activity of the nucleoid occlusion protein Noc.

Mol Cell 2021 Jul 9. Epub 2021 Jul 9.

Department of Molecular Microbiology, John Innes Centre, Norwich, NR4 7UH, UK. Electronic address:

ATP- and GTP-dependent molecular switches are extensively used to control functions of proteins in a wide range of biological processes. However, CTP switches are rarely reported. Here, we report that a nucleoid occlusion protein Noc is a CTPase enzyme whose membrane-binding activity is directly regulated by a CTP switch. Read More

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NMR identification of a conserved Drp1 cardiolipin-binding motif essential for stress-induced mitochondrial fission.

Proc Natl Acad Sci U S A 2021 Jul;118(29)

Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106;

Mitochondria form tubular networks that undergo coordinated cycles of fission and fusion. Emerging evidence suggests that a direct yet unresolved interaction of the mechanoenzymatic GTPase dynamin-related protein 1 (Drp1) with mitochondrial outer membrane-localized cardiolipin (CL), externalized under stress conditions including mitophagy, catalyzes essential mitochondrial hyperfragmentation. Here, using a comprehensive set of structural, biophysical, and cell biological tools, we have uncovered a CL-binding motif (CBM) conserved between the Drp1 variable domain (VD) and the unrelated ADP/ATP carrier (AAC/ANT) that intercalates into the membrane core to effect specific CL interactions. Read More

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The Fusion Between Autophagic Vesicles and Lysosomes.

Adv Exp Med Biol 2021 ;1208:55-66

Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The autophagosome delivers engulfed substrates to the lysosome for degradation via membrane fusion between the autophagosome and the lysosome. The process of membrane fusion is highly conserved in evolution. It is widely accepted that membrane fusion in general is driven by the zippering of the SNARE complex to form a four-helix bundle. Read More

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Era-like GTP protein gene expression in rice.

Braz J Biol 2021 9;82:e250700. Epub 2021 Jul 9.

Yangzhou University, The Ministry of Education of China, Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou, Jiangsu, China.

The mutations are genetic changes in the genome sequences and have a significant role in biotechnology, genetics, and molecular biology even to find out the genome sequences of a cell DNA along with the viral RNA sequencing. The mutations are the alterations in DNA that may be natural or spontaneous and induced due to biochemical reactions or radiations which damage cell DNA. There is another cause of mutations which is known as transposons or jumping genes which can change their position in the genome during meiosis or DNA replication. Read More

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Arabidopsis RAB8A, RAB8B, and RAB8D Proteins Interact with Several RTNLB Proteins and Are Involved in the Agrobacterium tumefaciens Infection Process.

Plant Cell Physiol 2021 Jul 14. Epub 2021 Jul 14.

Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan.

Arabidopsis thaliana small GTP-binding proteins, AtRAB8s, associate with the endomembrane system and modulate tubulovesicular trafficking between compartments of the biosynthetic and endocytic pathways. There are 5 members in Arabidopsis, namely AtRAB8A-8E. Yeast two-hybrid assays, bimolecular fluorescence complementation (BiFC) assays, and glutathione-S-transferase (GST) pull-down assays showed that RAB8A, 8B, and 8D interacted with several membrane-associated reticulon-like (AtRTNLB) proteins in yeast, plant cells, and in vitro. Read More

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TSC2 regulates lysosome biogenesis via a non-canonical RAGC and TFEB-dependent mechanism.

Nat Commun 2021 07 12;12(1):4245. Epub 2021 Jul 12.

Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Tuberous Sclerosis Complex (TSC) is caused by TSC1 or TSC2 mutations, resulting in hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1). Transcription factor EB (TFEB), a master regulator of lysosome biogenesis, is negatively regulated by mTORC1 through a RAG GTPase-dependent phosphorylation. Here we show that lysosomal biogenesis is increased in TSC-associated renal tumors, pulmonary lymphangioleiomyomatosis, kidneys from Tsc2 mice, and TSC1/2-deficient cells via a TFEB-dependent mechanism. Read More

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The interplay of Rac1 activity, ubiquitination and GDI binding and its consequences for endothelial cell spreading.

PLoS One 2021 12;16(7):e0254386. Epub 2021 Jul 12.

Department of Physiology, Amsterdam University Medical Centers, Amsterdam, The Netherlands.

Signaling by the Rho GTPase Rac1 is key to the regulation of cytoskeletal dynamics, cell spreading and adhesion. It is widely accepted that the inactive form of Rac1 is bound by Rho GDI, which prevents Rac1 activation and Rac1-effector interactions. In addition, GDI-bound Rac1 is protected from proteasomal degradation, in line with data showing that Rac1 ubiquitination occurs exclusively when Rac1 is activated. Read More

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Oryza sativa ObgC1 Acts as a Key Regulator of DNA Replication and Ribosome Biogenesis in Chloroplast Nucleoids.

Rice (N Y) 2021 Jul 12;14(1):65. Epub 2021 Jul 12.

Institute for New Rural Development, Sichuan Agricultural University, Yaan, 625000, China.

Background: The Spo0B-associated GTP-binding protein (Obg) GTPase, has diverse and important functions in bacteria, including morphological development, DNA replication and ribosome maturation. Homologs of the Bacillus subtilis Obg have been also found in chloroplast of Oryza sativa, but their primary roles remain unknown.

Results: We clarify that OsObgC1 is a functional homolog of AtObgC. Read More

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Crystal structure and characterization of nucleoside diphosphate kinase from Vibrio cholerae.

Biochimie 2021 Jul 7;190:57-69. Epub 2021 Jul 7.

Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, U.P., India. Electronic address:

Nucleoside diphosphate kinases (NDK) are ubiquitous enzymes that catalyse the transfer of the γ phosphate from nucleoside triphosphates (NTPs) to nucleoside diphosphate (NDPs), to maintain appropriate NTP levels in cells. NDKs are associated with signal transduction, cell development, proliferation, differentiation, tumor metastasis, apoptosis and motility. The critical role of NDK in bacterial virulence renders it a potential drug target. Read More

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FSH mediated cAMP signalling upregulates the expression of Gα subunits in pubertal rat Sertoli cells.

Biochem Biophys Res Commun 2021 Jul 5;569:100-105. Epub 2021 Jul 5.

Cellular Endocrinology Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, 110067, India; National Institute of Animal Biotechnology, Hyderabad, 500 032, Telangana, India. Electronic address:

Follicle Stimulating Hormone (FSH) acts via FSH-Receptor (FSH-R) by employing cAMP as the dominant secondary messenger in testicular Sertoli cells (Sc) to support spermatogenesis. Binding of FSH to FSH-R, results the recruitment of the intracellular GTP binding proteins, either stimulatory Gα or inhibitory Gα that in turn regulate cAMP production in Sc. The cytosolic concentration of cAMP being generated by FSH-R thereafter critically determines the downstream fate of the FSH signalling. Read More

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Insights into animal septins using recombinant human septin octamers with distinct SEPT9 isoforms.

J Cell Sci 2021 Jul 8. Epub 2021 Jul 8.

Institut Fresnel, CNRS UMR7249, Aix Marseille Univ, Centrale Marseille, 13013 Marseille, France.

Septin GTP-binding proteins contribute essential biological functions that range from the establishment of cell polarity to animal tissue morphogenesis. Human septins in cells form hetero-octameric septin complexes containing the ubiquitously expressed SEPT9. Despite the established role of SEPT9 in mammalian development and human pathophysiology, biochemical and biophysical studies have relied on monomeric SEPT9 thus not recapitulating its native assembly into hetero-octameric complexes. Read More

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Cdc42 localized in the CatSper signaling complex regulates cAMP-dependent pathways in mouse sperm.

FASEB J 2021 08;35(8):e21723

Instituto de Biología y Medicina Experimental (IBYME-CONICET), Ciudad Autónoma de Buenos Aires, Argentina.

Sperm acquire the ability to fertilize in a process called capacitation and undergo hyperactivation, a change in the motility pattern, which depends on Ca transport by CatSper channels. CatSper is essential for fertilization and it is subjected to a complex regulation that is not fully understood. Here, we report that similar to CatSper, Cdc42 distribution in the principal piece is confined to four linear domains and this localization is disrupted in CatSper1-null sperm. Read More

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Novel MAPK/AKT-impairing germline NRAS variant identified in a melanoma-prone family.

Fam Cancer 2021 Jul 3. Epub 2021 Jul 3.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, EPS 7106, Bethesda, MD, 20892, USA.

While several high-penetrance melanoma risk genes are known, variation in these genes fail to explain melanoma susceptibility in a large proportion of high-risk families. As part of a melanoma family sequencing study, including 435 families from Mediterranean populations we identified a novel NRAS variant (c.170A > C, p. Read More

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Astrocytes close the mouse critical period for visual plasticity.

Science 2021 07;373(6550):77-81

Center for Interdisciplinary Research in Biology, Collège de France, CNRS UMR 7241, INSERM U1050, Labex Memolife, PSL Research University, Paris, France.

Brain postnatal development is characterized by critical periods of experience-dependent remodeling of neuronal circuits. Failure to end these periods results in neurodevelopmental disorders. The cellular processes defining critical-period timing remain unclear. Read More

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RAB10 Interacts with ABCB4 and Regulates Its Intracellular Traffic.

Int J Mol Sci 2021 Jun 30;22(13). Epub 2021 Jun 30.

Inserm, Université Paris-Saclay, Physiopathogénèse et Traitement des Maladies du Foie, UMR_S 1193, Hepatinov, 91400 Orsay, France.

ABCB4 (ATP-binding cassette subfamily B member 4) is an ABC transporter expressed at the canalicular membrane of hepatocytes where it ensures phosphatidylcholine secretion into bile. Genetic variations of ABCB4 are associated with several rare cholestatic diseases. The available treatments are not efficient for a significant proportion of patients with ABCB4-related diseases and liver transplantation is often required. Read More

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Mechanism of Guanosine Triphosphate Hydrolysis by the Visual Proteins Arl3-RP2: Free Energy Reaction Profiles Computed with Ab Initio Type QM/MM Potentials.

Molecules 2021 Jun 30;26(13). Epub 2021 Jun 30.

Chemistry Department, M.V. Lomonosov Moscow State University, Leninskie Gory 1/3, 119991 Moscow, Russia.

We report the results of calculations of the Gibbs energy profiles of the guanosine triphosphate (GTP) hydrolysis by the Arl3-RP2 protein complex using molecular dynamics (MD) simulations with ab initio type QM/MM potentials. The chemical reaction of GTP hydrolysis to guanosine diphosphate (GDP) and inorganic phosphate (Pi) is catalyzed by GTPases, the enzymes, which are responsible for signal transduction in live cells. A small GTPase Arl3, catalyzing the GTP → GDP reaction in complex with the activating protein RP2, constitute an essential part of the human vision cycle. Read More

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Transcriptional Profiling Identifies Upregulation of Neuroprotective Pathways in Retinitis Pigmentosa.

Int J Mol Sci 2021 Jun 11;22(12). Epub 2021 Jun 11.

Institute of Anatomy and Cell Biology, Julius-Maximilians-University Wuerzburg, Koellikerstr. 6, D-97070 Würzburg, Germany.

Hereditary retinal degenerations like retinitis pigmentosa (RP) are among the leading causes of blindness in younger patients. To enable in vivo investigation of cellular and molecular mechanisms responsible for photoreceptor cell death and to allow testing of therapeutic strategies that could prevent retinal degeneration, animal models have been created. In this study, we deeply characterized the transcriptional profile of mice carrying the transgene rhodopsin V20G/P23H/P27L (VPP), which is a model for autosomal dominant RP. Read More

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Intraductal Papillary Mucinous Carcinoma Versus Conventional Pancreatic Ductal Adenocarcinoma: A Comprehensive Review of Clinical-Pathological Features, Outcomes, and Molecular Insights.

Int J Mol Sci 2021 Jun 23;22(13). Epub 2021 Jun 23.

INSERM UMRS_938, Microsatellite Instability and Cancer, Saint-Antoine Research Center, SIRIC CURAMUS, Sorbonne University, 75012 Paris, France.

Intraductal papillary mucinous neoplasms (IPMN) are common and one of the main precursor lesions of pancreatic ductal adenocarcinoma (PDAC). PDAC derived from an IPMN is called intraductal papillary mucinous carcinoma (IPMC) and defines a subgroup of patients with ill-defined specificities. As compared to conventional PDAC, IPMCs have been associated to clinical particularities and favorable pathological features, as well as debated outcomes. Read More

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Drugging the Undruggable: Advances on RAS Targeting in Cancer.

Genes (Basel) 2021 Jun 10;12(6). Epub 2021 Jun 10.

Oncogene Biology Laboratory, Francis Crick Institute, London NW1 1AT, UK.

Around 20% of all malignancies harbour activating mutations in RAS isoforms. Despite this, there is a deficiency of RAS-targeting agents licensed for therapeutic use. The picomolar affinity of RAS for GTP, and the lack of suitable pockets for high-affinity small-molecule binding, precluded effective therapies despite decades of research. Read More

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The Multifaceted Role of HSF1 in Pathophysiology: Focus on Its Interplay with TG2.

Int J Mol Sci 2021 Jun 14;22(12). Epub 2021 Jun 14.

Institute of Cytology, 194064 Saint-Petersburg, Russia.

The cellular environment needs to be strongly regulated and the maintenance of protein homeostasis is crucial for cell function and survival. HSF1 is the main regulator of the heat shock response (HSR), the master pathway required to maintain proteostasis, as involved in the expression of the heat shock proteins (HSPs). HSF1 plays numerous physiological functions; however, the main role concerns the modulation of HSPs synthesis in response to stress. Read More

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Transglutaminase 2 Inhibition for Prevention of Mucosal Damage in Celiac Disease.

Bana Jabri

N Engl J Med 2021 07;385(1):76-77

From the Departments of Medicine, Pathology, and Pediatrics, University of Chicago, Chicago.

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A Randomized Trial of a Transglutaminase 2 Inhibitor for Celiac Disease.

N Engl J Med 2021 07;385(1):35-45

From the Institute of Translational Immunology and Celiac Center, Research Center for Immune Therapy, University Medical Center, Johannes Gutenberg University, Mainz (D.S., T.F.-S.), the Department of Internal and Integrative Medicine, Sozialstiftung Bamberg, Bamberg (J.L.), the Department of Integrative Medicine, University of Duisburg-Essen, Duisburg-Essen (J.L.), the Division of Gastroenterology, Hepatology, and Infectious Diseases, Department of Internal Medicine I, University Hospital Tübingen, Tübingen (S.F.), the Department of Gastroenterology, Infectious Diseases, and Rheumatology, Campus Benjamin Franklin, Charité-University Medicine Berlin, Berlin (M. Schumann), the Department of Medicine II, University Hospital, Ludwig Maximilians University, Munich (H.P.T.), the Department of Medicine 1, Hector Center for Nutrition, Exercise, and Sports, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen (Y.Z.), the Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg (A.W.L.), the Department of Internal Medicine IV, University Hospital, Friedrich-Schiller University Jena, Jena (A.S.), and Dr. Falk Pharma, Freiburg (R.M., R.G.) - all in Germany; the Division of Gastroenterology and Celiac Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (D.S.); the Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital (M.M., A.P., M.-L.L.), the Faculty of Medicine and Health Technology, Tampere University (J.I., J.T.), Jilab (J.I.), and the Department of Pediatrics, Tampere University Hospital (M.-L.L.), Tampere, the Department of Internal Medicine, Central Finland Central Hospital, Jyväskylä (J.T.), Lääkärikeskus Aava Helsinki Kamppi, Helsinki (J. Koskenpato), and Clinical Research Services Turku, Turku (M. Scheinin) - all in Finland; Oslo University Hospital, Rikshospitalet, and Stiftelsen K.G. Jebsen Celiac Disease Research Center, University of Oslo, Oslo (K.E.A.L.), the Medical Department, Innlandet Hospital Trust, Gjøvik (O.H.), and Akershus University Hospital, Lørenskog (J.J.) - all in Norway; the University of Medicine and Pharmacy "Carol Davila" and the National Institute for Mother and Child Health "Alessandrescu-Rusescu," Bucharest, Romania (A.P.); the Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania (J. Kupcinskas); the Department of Gastroenterology, Internal Medicine Clinic, Tartu University Hospital, Tartu, Estonia (K.K.); the Department of Gastroenterology and Hepatology, University Hospital Zurich (L.B., J.Z.), and the Swiss Celiac Center, Center of Gastroenterology, Clinic Hirslanden (J.Z.) - both in Zurich, Switzerland; and University College Hospital Galway, Galway, Ireland (V.B.).

Background: In celiac disease, small intestinal transglutaminase 2 causes deamidation of glutamine residues in gluten peptides, which enhances stimulation of T cells and leads to mucosal injury. Inhibition of transglutaminase 2 is a potential treatment for celiac disease.

Methods: In a proof-of-concept trial, we assessed the efficacy and safety of a 6-week treatment with ZED1227, a selective oral transglutaminase 2 inhibitor, at three dose levels as compared with placebo, in adults with well-controlled celiac disease who underwent a daily gluten challenge. Read More

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Developmentally regulated GTP-binding protein 2 levels in prostate cancer cell lines impact docetaxel-induced apoptosis.

Investig Clin Urol 2021 Jul;62(4):485-495

Department of Urology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.

Purpose: This study aimed to confirm the association between developmentally regulated GTP-binding protein 2 (DRG2) expression and docetaxel-induced apoptosis and to determine whether prostate cancer responses to docetaxel treatment differ with DRG2 expression.

Materials And Methods: PC3, DU145, and LNCaP prostate cancer cell lines were used. The MTT assay was used to determine cell viability. Read More

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CNKSR1 serves as a scaffold to activate an EGFR phosphatase via exclusive interaction with RhoB-GTP.

Life Sci Alliance 2021 Sep 29;4(9). Epub 2021 Jun 29.

Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Toon, Japan

Epidermal growth factor receptor (EGFR) and human EGFR 2 (HER2) phosphorylation drives HER2-positive breast cancer cell proliferation. Enforced activation of phosphatases for those receptors could be a therapeutic option for HER2-positive breast cancers. Here, we report that degradation of an endosomal small GTPase, RhoB, by the ubiquitin ligase complex cullin-3 (CUL3)/KCTD10 is essential for both EGFR and HER2 phosphorylation in HER2-positive breast cancer cells. Read More

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September 2021

[Autosomal dominant spastic paraplegias].

Zh Nevrol Psikhiatr Im S S Korsakova 2021 ;121(5):75-87

Bochkov Research Center for Medical Genetics, Moscow, Russia.

Objective: To estimate the proportion and spectrum of infrequent autosomal dominant spastic paraplegias in a group of families with DNA-confirmed diagnosis and to investigate their molecular and clinical characteristics.

Material And Methods: Ten families with 6 AD-SPG: SPG6 (=1), SPG8 (=2), SPG9A (=1), SPG12 (=1), SPG17 (=3), SPG31 (=2) were studied using clinical, genealogical, molecular-genetic (massive parallel sequencing, spastic paraplegia panel, whole-exome sequencing, multiplex ligation-dependent amplification, Sanger sequencing) and bioinformatic methods.

Results And Conclusion: Nine heterozygous mutations were detected in 6 genes, including the common mutation p. Read More

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A nuclear proteome localization screen reveals the exquisite specificity of Gpn2 in RNA polymerase biogenesis.

Cell Cycle 2021 Jun 28:1-13. Epub 2021 Jun 28.

Terry Fox Laboratories, BC Cancer Research Institute, Vancouver, Canada.

The GPN proteins are a conserved family of GTP-binding proteins that are involved in the assembly and subsequent import of RNA polymerase II and III. In this study, we sought to ascertain the specificity of yeast GPN2 for RNA polymerases by screening the localization of a collection of 1350 GFP-tagged nuclear proteins in WT or mutant cells. We found that the strongest mislocalization occurred for RNA polymerase II and III subunits and only a handful of other RNAPII associated proteins were altered in mutant cells. Read More

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Rab3a, a small GTP-binding protein, is required for the stabilization of the murine leukaemia virus gag protein.

Small GTPases 2021 Jun 27:1-21. Epub 2021 Jun 27.

Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.

We recently identified a CD63-interacting protein to understand the role of CD63 in virion production of the human immunodeficiency virus type 1, and we have found that Rab3a forms a complex with CD63. In this study, we analysed the effect of Rab3a on virion production of the murine leukaemia virus (MLV), which is another member of the retrovirus family. We found that Rab3a silencing induced lysosomal degradation of the MLV Gag protein, and recovery of the Rab3a expression restored the level of the Gag protein through a complex formation of MLV Gag and Rab3a, indicating that Rab3a is required for MLV Gag protein expression. Read More

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