The Rho Guanine Nucleotide Exchange Factors Intersectin 1L and β-Pix Control Calcium-Regulated Exocytosis in Neuroendocrine PC12 Cells
GTPases of the Rho family are molecular switches that play an important role in a wide range of membrane-trafficking processes including neurotransmission and hormone release. We have previously demonstrated that RhoA and Cdc42 regulate calcium-dependent exocytosis in chromaffin cells by controlling actin dynamics, whereas Rac1 regulates lipid organisation. These findings raised the question of the upstream mechanism activating these GTPases during exocytosis. The guanine nucleotide exchange factors (GEFs) that catalyse the exchange of GDP for GTP are crucial elements regulating Rho signalling. Using an RNA interference approach, we have recently demonstrated that the GEFs Intersectin-1L and β-Pix, play essential roles in neuroendocrine exocytosis by controlling the activity of Cdc42 and Rac1, respectively. This review summarizes these results and discusses the functional importance of Rho GEFs in the exocytotic machinery in neuroendocrine cells.
KeywordsPC12 cells Calcium-regulated exocytosis Rho Guanine nucleotide exchange factor β-Pix Intersectin Cancer
We wish to thank Dr. Nancy Grant for critical reading of the manuscript. The work presented in this review was supported by a Human Frontier Science Program (HFSP) grant (RGY40-2003C), an ANR grant (ANR-07-JCJC-088-01), a ‘Association pour la Recherche sur le Cancer’ grant (ARC #1055) to S.G, an ANR grant (ANR-09-BLAN-0264-01) and a ‘Association pour la Recherche sur le Cancer’ grant (ARC #4051) to N.V as well as by the ‘Fondation pour la Recherche Médicale’ (FRM, fellowship to M.C.).
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