Journal
CELLULAR AND MOLECULAR NEUROBIOLOGY
Volume 30, Issue 8, Pages 1327-1333Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10571-010-9580-2
Keywords
PC12 cells; Calcium-regulated exocytosis; Rho; Guanine nucleotide exchange factor; beta-Pix; Intersectin; Cancer
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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 de:demonstrated that the GEFs lntersectin-1L and beta-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.
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