Format

Send to

Choose Destination
Nat Commun. 2020 Mar 9;11(1):1266. doi: 10.1038/s41467-020-14993-8.

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

Author information

1
European Neuroscience Institute-A Joint Initiative of the University Medical Center Göttingen and the Max Planck Society Göttingen, Göttingen, Germany.
2
University of Copenhagen, Department for Neuroscience, Faculty of Health and Medical Sciences, Copenhagen, Denmark.
3
Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
4
Leibniz Research Institute for Molecular Pharmacology, Molecular Physiology and Cell Biology Section, Berlin, Germany.
5
Department of Clinical Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam UMC, Amsterdam, The Netherlands.
6
Institute for Cellular Biochemistry, University Medical Center Göttingen (UMG), Göttingen, Germany.
7
University of Copenhagen, Department for Neuroscience, Faculty of Health and Medical Sciences, Copenhagen, Denmark. jakobbs@sund.ku.dk.
8
European Neuroscience Institute-A Joint Initiative of the University Medical Center Göttingen and the Max Planck Society Göttingen, Göttingen, Germany. imilose@gwdg.de.

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center