Involvement of the Rab27 binding protein Slac2c/MyRIP in insulin exocytosis

Laurent Waselle, Thierry Coppola, Mitsunori Fukuda, Mariella Iezzi, Aziz El-Amraoui, Christine Petit, Romano Regazzi

Research output: Contribution to journalArticlepeer-review

127 Citations (Scopus)

Abstract

Rab27a is a GTPase associated with insulin-containing secretory granules of pancreatic β-cells. Selective reduction of Rab27a expression by RNA interference did not alter granule distribution and basal secretion but impaired exocytosis triggered by insulin secretagogues. Screening for potential effectors of the GTPase revealed that the Rab27a-binding protein Slac2c/MyRIP is associated with secretory granules of β-cells. Attenuation of Slac2c/MyRIP expression by RNA interference did not modify basal secretion but severely impaired hormone release in response to secretagogues. Although β-cells express Myosin-Va, a potential partner of Slac2c/MyRIP, no functional link between the two proteins could be demonstrated. In fact, overexpression of the Myosin-Va binding domain of Slac2c/MyRIP did not affect granule localization and hormone exocytosis. In contrast, overexpression of the actin-binding domain of Slac2c/MyRIP led to a potent inhibition of exocytosis without detectable alteration in granule distribution. This effect was prevented by point mutations that abolish actin binding. Taken together our data suggest that Rab27a and Slac2c/MyRIP are part of a complex mediating the interaction of secretory granules with cortical actin cytoskeleton and participate to the regulation of the final steps of insulin exocytosis.

Original languageEnglish
Pages (from-to)4103-4113
Number of pages11
JournalMolecular biology of the cell
Volume14
Issue number10
DOIs
Publication statusPublished - 2003 Oct 1
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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