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

Alejandra Tomas, Barbara Yermen, Romano Regazzi, Jeffrey E. Pessin, Philippe A. Halban

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The role of PIP2 in pancreatic beta cell function was examined here using the beta cell line MIN6B1. Blocking PIP2 with PH-PLC-GFP or PIP5KIγ RNAi did not impact on glucose-stimulated secretion although susceptibility to apoptosis was increased. Over-expression of PIP5KIγ improved cell survival and inhibited secretion with accumulation of endocytic vacuoles containing F-actin, PIP2, 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. PIP2 co-localized with gelsolin and F-actin, and gelsolin co-expression partially reversed the secretory defect of PIP5KIγ-over-expressing cells. RhoA/ROCK inhibition increased actin depolymerization and secretion, which was prevented by over-expressing PIP5KIγ, while blocking PIP2 reduced constitutively active RhoA V14-induced F-actin polymerization. In conclusion, although PIP2 plays a pro-survival role in MIN6B1 cells, excessive PIP2 production because of PIP5KIγ over-expression inhibits secretion because of both a defective Arf6/PIP5KIγ-dependent endocytic recycling of secretory membrane and secretory membrane components such as phogrin and the RhoA/ROCK/PIP5KIγ-dependent perturbation of F-actin cytoskeleton remodelling.

Original languageEnglish (US)
Pages (from-to)123-137
Number of pages15
JournalTraffic
Volume11
Issue number1
DOIs
StatePublished - Jan 2010

Fingerprint

Phosphatidylinositols
Actins
Insulin
Gelsolin
Programmable logic controllers
Vacuoles
Cells
Secretory Component
Membranes
Caveolin 1
Depolymerization
Transferrin Receptors
Insulin-Secreting Cells
RNA Interference
Actin Cytoskeleton
Polymerization
Recycling
Cell Survival
Membrane Proteins
Apoptosis

Keywords

  • Arf6
  • Endocytic recycling
  • F-actin
  • Insulin secretion
  • PIP5KIγ
  • PIP
  • RhoA/ROCK

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Structural Biology
  • Molecular Biology
  • Genetics

Cite this

Regulation of insulin secretion by phosphatidylinositol-4,5-bisphosphate. / Tomas, Alejandra; Yermen, Barbara; Regazzi, Romano; Pessin, Jeffrey E.; Halban, Philippe A.

In: Traffic, Vol. 11, No. 1, 01.2010, p. 123-137.

Research output: Contribution to journalArticle

Tomas, Alejandra ; Yermen, Barbara ; Regazzi, Romano ; Pessin, Jeffrey E. ; Halban, Philippe A. / Regulation of insulin secretion by phosphatidylinositol-4,5-bisphosphate. In: Traffic. 2010 ; Vol. 11, No. 1. pp. 123-137.
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