Endophilin-A Coordinates Priming and Fusion of Neurosecretory Vesicles Via Intersectin

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Mar 11

PMID 32152276

Citations 14

Authors

Sindhuja Gowrisankaran

Sebastien Houy

Johanna G Pena Del Castillo

Vicky Steubler

Monika Gelker

Jana Kroll

Paulo S Pinheiro

Dirk Schwitters

Nils Halbsgut

Arndt Pechstein

Jan R T van Weering

Tanja Maritzen

Volker Haucke

Nuno Raimundo

Jakob B Sorensen

Ira Milosevic

Affiliations

Soon will be listed here.

Abstract

Endophilins-A are conserved endocytic adaptors with membrane curvature-sensing and -inducing properties. We show here that, independently of their role in endocytosis, endophilin-A1 and endophilin-A2 regulate exocytosis of neurosecretory vesicles. The number and distribution of neurosecretory vesicles were not changed in chromaffin cells lacking endophilin-A, yet fast capacitance and amperometry measurements revealed reduced exocytosis, smaller vesicle pools and altered fusion kinetics. The levels and distributions of the main exocytic and endocytic factors were unchanged, and slow compensatory endocytosis was not robustly affected. Endophilin-A's role in exocytosis is mediated through its SH3-domain, specifically via a direct interaction with intersectin-1, a coordinator of exocytic and endocytic traffic. Endophilin-A not able to bind intersectin-1, and intersectin-1 not able to bind endophilin-A, resulted in similar exocytic defects in chromaffin cells. Altogether, we report that two endocytic proteins, endophilin-A and intersectin-1, are enriched on neurosecretory vesicles and regulate exocytosis by coordinating neurosecretory vesicle priming and fusion.

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