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

Author

Listed:
  • 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
    University of Coimbra)

  • 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)

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.

Suggested Citation

  • 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. Wee, 2020. "Endophilin-A coordinates priming and fusion of neurosecretory vesicles via intersectin," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14993-8
    DOI: 10.1038/s41467-020-14993-8
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