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Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc...

Tawfik, Bassam; Martins, Joana S; Houy, Sébastien; Imig, Cordelia; Pinheiro, Paulo S.; Wojcik, Sonja M; Brose, Nils; Cooper, Benjamin H

Synaptotagmins confer calcium-dependence to the exocytosis of secretory vesicles, but how coexpressed synaptotagmins interact remains unclear. We find that synaptotagmin-1 and synaptotagmin-7 when present alone act as standalone fast and slow Ca2+-sensors for vesicle fusion in mouse chromaffin cells. When present together, synaptotagmin-1 and synaptotagmin-7 are found in largely non-overlapping clusters on dens...


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

Gowrisankaran, Sindhuja; Houy, Sébastien; Del Castillo, Johanna G Peña; Steubler, Vicky; Gelker, Monika; Kroll, Jana; Pinheiro, Paulo S.

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 re...


Doc2B acts as a calcium sensor for vesicle priming requiring synaptotagmin-1, M...

Houy, Sébastien; Groffen, Alexander J; Ziomkiewicz, Iwona; Verhage, Matthijs; Pinheiro, Paulo S.; Sørensen, Jakob Balslev

Doc2B is a cytosolic protein with binding sites for Munc13 and Tctex-1 (dynein light chain), and two C2-domains that bind to phospholipids, Ca2+ and SNAREs. Whether Doc2B functions as a calcium sensor akin to synaptotagmins, or in other calcium-independent or calcium-dependent capacities is debated. We here show by mutation and overexpression that Doc2B plays distinct roles in two sequential priming steps in mo...


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