αII-spectrin controls calcium-regulated exocytosis in neuroendocrine chromaffin cells through neuronal Wiskott-Aldrich Syndrome protein interaction.

Fiche publication

Date publication

décembre 2019

Journal

IUBMB life

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BADER Marie-France , Dr GASMAN Stéphane , Dr VITALE Nicolas , Dr ORY Stéphane

Tous les auteurs :
Houy S, Nicolas G, Momboisse F, Malacombe M, Bader MF, Vitale N, Lecomte MC, Ory S, Gasman S

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/31859439

Résumé

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.