Séverine Cheviet

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The small GTPases Rab3 and Rab27 are associated with secretory granules of pancreatic beta-cells and regulate insulin exocytosis. In this study, we investigated the role of Noc2, a potential partner of these two GTPases, in insulin secretion. In the beta-cell line INS-1E wild-type Noc2, Noc265E, and Noc258A, a mutant capable of interacting with Rab27 but(More)
The GTPases Rab3a and Rab27a and their effectors Granuphilin/Slp4 and Noc2 are essential regulators of neuroendocrine secretion. Chronic exposure of pancreatic beta-cells to supraphysiological glucose levels decreased selectively the expression of these proteins. This glucotoxic effect was mimicked by cAMP-raising agents and blocked by PKA inhibitors. We(More)
The Rab GTPase effector Noc2 was brought into the limelight by a recent publication that demonstrated its requirements at different stages of regulated exocytosis. Noc2 knockout resulted in distinct abnormalities in endocrine and exocrine cells, ranging from the accumulation of secretory granules of increased size to impairments in the regulated release of(More)
Although the assembly of a ternary complex between the SNARE proteins syntaxin-1, SNAP25 and VAMP2 is known to be crucial for insulin exocytosis, the mechanisms controlling this key event are poorly understood. We found that pancreatic beta-cells express different isoforms of tomosyn-1, a syntaxin-1-binding protein possessing a SNARE-like motif. Using(More)
Introduction Insulin secretion from pancreatic -cells is an essential prerequisite to maintain appropriate blood glucose levels. Defects in this process can result in profound metabolic disorders and, eventually, lead to diabetes mellitus. The molecular mechanism regulating the fusion of insulincontaining secretory granules with the plasma membrane are(More)
Rab3 and Rab27 GTPases control late events in the secretory pathway of mammalian cells including docking and fusion of secretory vesicles with the plasma membrane. The action of Rab3 and Rab27 on the exocytotic process is exerted through the activation of specific effectors. Several proteins with the capacity to interact in a GTP-dependent manner with Rab3(More)
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