Regulation of insulin secretion by phosphatidylinositol-4,5-bisphosphate.

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Version: author
Serval ID
serval:BIB_894827BF5F6C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Regulation of insulin secretion by phosphatidylinositol-4,5-bisphosphate.
Journal
Traffic
Author(s)
Tomas A., Yermen B., Regazzi R., Pessin J.E., Halban P.A.
ISSN
1600-0854[electronic], 1398-9219[linking]
Publication state
Published
Issued date
2010
Peer-reviewed
Oui
Volume
11
Number
1
Pages
123-137
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
The role of PIP(2) in pancreatic beta cell function was examined here using the beta cell line MIN6B1. Blocking PIP(2) with PH-PLC-GFP or PIP5KIgamma RNAi did not impact on glucose-stimulated secretion although susceptibility to apoptosis was increased. Over-expression of PIP5KIgamma improved cell survival and inhibited secretion with accumulation of endocytic vacuoles containing F-actin, PIP(2), transferrin receptor, caveolin 1, Arf6 and the insulin granule membrane protein phogrin but not insulin. Expression of constitutively active Arf6 Q67L also resulted in vacuole formation and inhibition of secretion, which was reversed by PH-PLC-GFP co-expression. PIP(2) co-localized with gelsolin and F-actin, and gelsolin co-expression partially reversed the secretory defect of PIP5KIgamma-over-expressing cells. RhoA/ROCK inhibition increased actin depolymerization and secretion, which was prevented by over-expressing PIP5KIgamma, while blocking PIP(2) reduced constitutively active RhoA V14-induced F-actin polymerization. In conclusion, although PIP(2) plays a pro-survival role in MIN6B1 cells, excessive PIP(2) production because of PIP5KIgamma over-expression inhibits secretion because of both a defective Arf6/PIP5KIgamma-dependent endocytic recycling of secretory membrane and secretory membrane components such as phogrin and the RhoA/ROCK/PIP5KIgamma-dependent perturbation of F-actin cytoskeleton remodelling.
Keywords
Animals, Apoptosis/drug effects, Blotting, Western, Cell Culture Techniques, Cell Line, Cell Survival/drug effects, Electrophoresis, Polyacrylamide Gel, Endocytosis/drug effects, Glucose/pharmacology, In Situ Nick-End Labeling, Insulin/secretion, Insulin-Secreting Cells/drug effects, Insulin-Secreting Cells/enzymology, Mice, Microscopy, Confocal, Microscopy, Fluorescence, Phosphatidylinositol 4,5-Diphosphate/antagonists & inhibitors, Phosphatidylinositol 4,5-Diphosphate/physiology, Phosphotransferases (Alcohol Group Acceptor)/antagonists & inhibitors, Phosphotransferases (Alcohol Group Acceptor)/biosynthesis, Protein Transport, Vacuoles/drug effects, Vacuoles/enzymology
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2010 11:41
Last modification date
20/08/2019 14:48
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