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

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 activati...

Full description

Saved in:
Bibliographic Details
Published in:The EMBO journal 2006-08, Vol.25 (15), p.3494-3503
Main Authors: Malacombe, Magali, Ceridono, Mara, Calco, Valérie, Chasserot-Golaz, Sylvette, McPherson, Peter S, Bader, Marie-France, Gasman, Stéphane
Format: Article
Language:English
Subjects:
Actins - metabolism
Adaptor Proteins, Vesicular Transport - metabolism
Animals
Calcium - metabolism
Cdc42
cdc42 GTP-Binding Protein - metabolism
Cell adhesion & migration
Cellular Biology
Chromaffin Cells - cytology
Chromaffin Cells - metabolism
Cytoskeleton
EMBO20
endocrine cells
exocytosis
Exocytosis - physiology
Guanine Nucleotide Exchange Factors - metabolism
Humans
intersectin
Life Sciences
Membranes
Microscopy, Confocal
Neurons
PC12 Cells
Proteins
Rats
secretion
Secretory Vesicles - metabolism
Signal transduction
Signal Transduction - physiology
Transfection
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0261-4189
1460-2075
DOI:10.1038/sj.emboj.7601247