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

Sindhuja Gowrisankaran, Sébastien Houy, Johanna G. Peña Castillo, Vicky Steubler, Monika Gelker, Jana Kroll, Paulo S. Pinheiro, Dirk Schwitters, Nils Halbsgut, Arndt Pechstein, Jan R. T. Weering, Tanja Maritzen, Volker Haucke, Nuno Raimundo, Jakob B. Sørensen () and Ira Milosevic ()
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Sindhuja Gowrisankaran: European Neuroscience Institute—A Joint Initiative of the University Medical Center Göttingen and the Max Planck Society Göttingen
Sébastien Houy: University of Copenhagen, Department for Neuroscience, Faculty of Health and Medical Sciences
Johanna G. Peña Castillo: European Neuroscience Institute—A Joint Initiative of the University Medical Center Göttingen and the Max Planck Society Göttingen
Vicky Steubler: European Neuroscience Institute—A Joint Initiative of the University Medical Center Göttingen and the Max Planck Society Göttingen
Monika Gelker: European Neuroscience Institute—A Joint Initiative of the University Medical Center Göttingen and the Max Planck Society Göttingen
Jana Kroll: European Neuroscience Institute—A Joint Initiative of the University Medical Center Göttingen and the Max Planck Society Göttingen
Paulo S. Pinheiro: University of Copenhagen, Department for Neuroscience, Faculty of Health and Medical Sciences
Dirk Schwitters: European Neuroscience Institute—A Joint Initiative of the University Medical Center Göttingen and the Max Planck Society Göttingen
Nils Halbsgut: European Neuroscience Institute—A Joint Initiative of the University Medical Center Göttingen and the Max Planck Society Göttingen
Arndt Pechstein: Molecular Physiology and Cell Biology Section
Jan R. T. Weering: Amsterdam UMC
Tanja Maritzen: Molecular Physiology and Cell Biology Section
Volker Haucke: Molecular Physiology and Cell Biology Section
Nuno Raimundo: University Medical Center Göttingen (UMG)
Jakob B. Sørensen: University of Copenhagen, Department for Neuroscience, Faculty of Health and Medical Sciences
Ira Milosevic: European Neuroscience Institute—A Joint Initiative of the University Medical Center Göttingen and the Max Planck Society Göttingen

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-14993-8

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