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

2020 | journal article; overview. A publication with affiliation to the University of Göttingen.

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​Endophilin-A coordinates priming and fusion of neurosecretory vesicles via intersectin​
Gowrisankaran, S.; Houy, S.; del Castillo, J. G. P.; Steubler, V.; Gelker, M.; Kroll, J. & Pinheiro, P. S. et al.​ (2020) 
Nature Communications11(1) art. 1266​.​ DOI: https://doi.org/10.1038/s41467-020-14993-8 

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Authors
Gowrisankaran, Sindhuja; Houy, Sébastien; del Castillo, Johanna G. Peña; Steubler, Vicky; Gelker, Monika; Kroll, Jana; Pinheiro, Paulo S.; Schwitters, Dirk; Halbsgut, Nils; Pechstein, Arndt; van Weering, Jan R. T.; Maritzen, Tanja; Haucke, Volker; Raimundo, Nuno; Sørensen, Jakob B.; Milosevic, Ira
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.
Issue Date
2020
Journal
Nature Communications 
Project
SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente 
SFB 1190 | P02: Charakterisierung der ER-Mitochondrien-Kontakte und ihre Rolle in der Signalweiterleitung 
Organization
Universitätsmedizin Göttingen
Working Group
RG Milosevic (Synaptic Vesicle Dynamics) 
eISSN
2041-1723
Language
English
Sponsor
Open-Access-Publikationsfonds 2020

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