Endophilin-A coordinates priming and fusion of neurosecretory vesicles via intersectin

Sindhuja Gowrisankaran, Sébastien Houy, Johanna G.Peña 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. Sørensen, Ira Milosevic*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Article number1266
JournalNature Communications
Issue number1
Publication statusPublished - 1 Dec 2020

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