A role for Rab10 in von Willebrand factor release discovered by an AP-1 interactor screen in C. elegans

Autor: Grégoire Michaux, Thomas D. Nightingale, E. Gallaud, S. Nurrish, Clare E. F. Dyer, Daniel F. Cutler
Přispěvatelé: Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Laboratory for Molecular Cell Biology, University College of London [London] (UCL), De Villemeur, Hervé, Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2011
Předmět:
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology
MESH: RNA Interference
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Polymerase Chain Reaction
Clathrin
Cell Line
03 medical and health sciences
symbols.namesake
0302 clinical medicine
Von Willebrand factor
hemic and lymphatic diseases
MESH: Caenorhabditis elegans
von Willebrand Factor
Weibel–Palade body
Animals
Humans
Secretion
Small GTPase
MESH: Animals
MESH: von Willebrand Factor
Caenorhabditis elegans
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
030304 developmental biology
Clotting factor
0303 health sciences
MESH: Humans
biology
MESH: Polymerase Chain Reaction
[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Hematology
Golgi apparatus
MESH: Transcription Factor AP-1
Cell biology
MESH: Cell Line
Transcription Factor AP-1
MESH: rab GTP-Binding Proteins
rab GTP-Binding Proteins
Aftiphilin
biology.protein
symbols
RNA Interference
Endothelium
Vascular
MESH: Endothelium
Vascular
030217 neurology & neurosurgery
Zdroj: Journal of Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis, 2011, 9 (2), pp.392-401. ⟨10.1111/j.1538-7836.2010.04138.x⟩
Journal of Thrombosis and Haemostasis, Wiley, 2011, 9 (2), pp.392-401. ⟨10.1111/j.1538-7836.2010.04138.x⟩
ISSN: 1538-7933
1538-7836
DOI: 10.1111/j.1538-7836.2010.04138.x⟩
Popis: International audience; BACKGROUND: Endothelial von Willebrand factor (VWF) mediates platelet adhesion and acts as a protective chaperone to clotting factor VIII. Rapid release of highly multimerized VWF is particularly effective in promoting hemostasis. To produce this protein, an elaborate biogenesis is required, culminating at the trans-Golgi network (TGN) in storage within secretory granules called Weibel-Palade bodies (WPB). Failure to correctly form these organelles can lead to uncontrolled secretion of low-molecular-weight multimers of VWF. The TGN-associated adaptor AP-1 and its interactors clathrin, aftiphilin and γ-synergin are essential to initial WPB formation at the Golgi apparatus, and thus to VWF storage and secretion. OBJECTIVES: To identify new proteins implicated in VWF storage and/or secretion. METHODS: A genomewide RNA interference (RNAi) screen was performed in the Nematode C. elegans to identify new AP-1 genetic interactors. RESULTS: The small GTPase Rab10 was found to genetically interact with a partial loss of function of AP-1 in C. elegans. We investigated Rab10 in human primary umbilical vein endothelial cells (HUVECs). We report that Rab10 is enriched at the Golgi apparatus, where WPB are formed, and that in cells where Rab10 expression has been suppressed by siRNA, VWF secretion is altered: the amount of rapidly released VWF was significantly reduced. We also found that Rab8A has a similar function. CONCLUSION: Rab10 and Rab8A are new cytoplasmic factors implicated in WPB biogenesis that play a role in generating granules that can rapidly respond to secretagogue.
Databáze: OpenAIRE
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