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Intersectin-1L nucleotide exchange factor regulates secretory granule exocytosis by activating Cdc42.

Authors: Malacombe, Magali  Ceridono, Mara  Calco, Valérie  Chasserot-Golaz, Sylvette  McPherson, Peter S  Bader, Marie-France  Gasman, Stéphane 
Citation: Malacombe M, etal., EMBO J. 2006 Aug 9;25(15):3494-503. doi: 10.1038/sj.emboj.7601247. Epub 2006 Jul 27.
Pubmed: (View Article at PubMed) PMID:16874303
DOI: Full-text: DOI:10.1038/sj.emboj.7601247

Rho GTPases are key regulators of the actin cytoskeleton in membrane trafficking events. We previously reported that Cdc42 facilitates exocytosis in neuroendocrine cells by stimulating actin assembly at docking sites for secretory granules. These findings raise the question of the mechanism activating Cdc42 in exocytosis. The neuronal guanine nucleotide exchange factor, intersectin-1L, which specifically activates Cdc42 and is at an interface between membrane trafficking and actin dynamics, appears as an ideal candidate to fulfill this function. Using PC12 and chromaffin cells, we now show the presence of intersectin-1 at exocytotic sites. Moreover, through an RNA interference strategy coupled with expression of various constructs encoding the guanine nucleotide exchange domain, we demonstrate that intersectin-1L is an essential component of the exocytotic machinery. Silencing of intersectin-1 prevents secretagogue-induced activation of Cdc42 revealing intersectin-1L as the factor integrating Cdc42 activation to the exocytotic pathway. Our results extend the current role of intersectin-1L in endocytosis to a function in exocytosis and support the idea that intersectin-1L is an adaptor that coordinates exo-endocytotic membrane trafficking in secretory cells.

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CRRD Object Information
CRRD ID: 13461861
Created: 2017-12-04
Species: All species
Last Modified: 2017-12-04
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.