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https://hdl.handle.net/10316/108139
Title: | Doc2B acts as a calcium sensor for vesicle priming requiring synaptotagmin-1, Munc13-2 and SNAREs | Authors: | Houy, Sébastien Groffen, Alexander J Ziomkiewicz, Iwona Verhage, Matthijs Pinheiro, Paulo S. Sørensen, Jakob Balslev |
Keywords: | adrenaline; capacitance measurements; chromaffin cell; exocytosis; membrane fusion; mouse; neuroscience | Issue Date: | 23-Dec-2017 | Publisher: | eLife Sciences Publications | Serial title, monograph or event: | eLife | Volume: | 6 | Abstract: | 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 mouse adrenal chromaffin cells. Mutating Ca2+-coordinating aspartates in the C2A-domain localizes Doc2B permanently at the plasma membrane, and renders an upstream priming step Ca2+-independent, whereas a separate function in downstream priming depends on SNARE-binding, Ca2+-binding to the C2B-domain of Doc2B, interaction with ubMunc13-2 and the presence of synaptotagmin-1. Another function of Doc2B - inhibition of release during sustained calcium elevations - depends on an overlapping protein domain (the MID-domain), but is separate from its Ca2+-dependent priming function. We conclude that Doc2B acts as a vesicle priming protein. | URI: | https://hdl.handle.net/10316/108139 | ISSN: | 2050-084X | DOI: | 10.7554/eLife.27000 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
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Doc2B acts as a calcium sensor for vesicle priming requiring synaptotagmin-1, munc13-2 and SNAREs.pdf | 4.6 MB | Adobe PDF | View/Open |
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