The Small GTPase RalA controls exocytosis of large dense core secretory granules by interacting with ARF6-dependent phospholipase D1.

Details

Serval ID
serval:BIB_38AFD6967AA1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The Small GTPase RalA controls exocytosis of large dense core secretory granules by interacting with ARF6-dependent phospholipase D1.
Journal
Journal of Biological Chemistry
Author(s)
Vitale N., Mawet J., Camonis J., Regazzi R., Bader M.F., Chasserot-Golaz S.
ISSN
0021-9258
Publication state
Published
Issued date
08/2005
Peer-reviewed
Oui
Volume
280
Number
33
Pages
29921-29928
Language
english
Notes
Publication types: Journal Article
Abstract
RalA and RalB constitute a family of highly similar Ras-related GTPases widely distributed in different tissues. Recently, active forms of Ral proteins have been shown to bind to the exocyst complex, implicating them in the regulation of cellular secretion. Since RalA is present on the plasma membrane in neuroendocrine chromaffin and PC12 cells, we investigated the potential role of RalA in calcium-regulated exocytotic secretion. We show here that endogenous RalA is activated during exocytosis. Expression of the constitutively active RalA (G23V) mutant enhances secretagogue-evoked secretion from PC12 cells. Conversely, expression of the constitutively inactive GDP-bound RalA (G26A) or silencing of the RalA gene by RNA interference led to a strong impairment of the exocytotic response. RalA was found to co-localize with phospholipase D1 (PLD1) at the plasma membrane in PC12 cells. We demonstrate that cell stimulation triggers a direct interaction between RalA and ARF6-activated PLD1. Moreover, reduction of endogenous RalA expression level interfered with the activation of PLD1 observed in secretagogue-stimulated cells. Finally, using various RalA mutants selectively impaired in their ability to activate downstream effectors, we show that PLD1 activation is essential for the activation of secretion by GTP-loaded RalA. Together, these results provide evidence that RalA is a positive regulator of calcium-evoked exocytosis of large dense core secretory granules and suggest that stimulation of PLD1 and consequent changes in plasma membrane phospholipid composition is the major function RalA undertakes in calcium-regulated exocytosis.
Keywords
ADP-Ribosylation Factors/physiology, Animals, Calcium/physiology, Exocytosis, Growth Hormone/secretion, PC12 Cells, Phospholipase D/physiology, RNA, Small Interfering/pharmacology, Rats, Secretory Vesicles/metabolism, ral GTP-Binding Proteins/analysis, ral GTP-Binding Proteins/physiology
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 14:29
Last modification date
20/08/2019 13:28
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