αII-spectrin controls calcium-regulated exocytosis in neuroendocrine chromaffin cells through neuronal Wiskott-Aldrich Syndrome protein interaction.
Besides a fundamental structural role at the plasma membrane, spectrin- and actin-based skeletons have been proposed to participate in various processes including vesicular trafficking. Neuroendocrine cells release hormones and neuropeptides through calcium-regulated exocytosis, a process that is coordinated by a fine remodeling of the actin cytoskeleton. We describe here that calcium-regulated exocytosis is impaired in chromaffin and PC12 cells with reduced αII-spectrin expression levels. Using yeast two-hybrid screening, we show that neuronal Wiskott-Aldrich Syndrome protein (N-WASP) is a partner of the αII-spectrin SH3 domain and demonstrate that secretagogue-evoked N-WASP recruitment at cell periphery is blocked in the absence of αII-spectrin. Additionally, experiments performed with ectopically expressed αII-spectrin mutant unable to bind N-WASP indicated that the interaction between SH3 domain and N-WASP is pivotal for neuroendocrine secretion. Our results extend the list of spectrin interactors and strengthen the idea that αII-spectrin is an important scaffold protein that gathers crucial actin-related players of the exocytic machinery.
['Houy|Sébastien|S|', 'Nicolas|Gaël|G|', 'Momboisse|Fanny|F|', 'Malacombe|Magali|M|', 'Bader|Marie-France|MF|', 'Vitale|Nicolas|N|0000-0002-4752-4907', 'Lecomte|Marie-Christine|MC|', 'Ory|Stéphane|S|0000-0003-4359-1157', 'Gasman|Stéphane|S|0000-0001-8415-1276']
D000818:Animals D002118:Calcium D002352:Carrier Proteins D002395:Catecholamines D002417:Cattle D019439:Chromaffin Cells D005089:Exocytosis D013006:Growth Hormone D008840:Microfilament Proteins D009154:Mutation D055099:Neuroendocrine Cells D016716:PC12 Cells D051381:Rats D020798:Two-Hybrid System Techniques D051317:Wiskott-Aldrich Syndrome Protein, Neuronal D018909:src Homology Domains
exocytosis N-WASP spectrin PC12 and chromaffin cells