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https://hdl.handle.net/10316/108139
Título: | Doc2B acts as a calcium sensor for vesicle priming requiring synaptotagmin-1, Munc13-2 and SNAREs | Autor: | Houy, Sébastien Groffen, Alexander J Ziomkiewicz, Iwona Verhage, Matthijs Pinheiro, Paulo S. Sørensen, Jakob Balslev |
Palavras-chave: | adrenaline; capacitance measurements; chromaffin cell; exocytosis; membrane fusion; mouse; neuroscience | Data: | 23-Dez-2017 | Editora: | eLife Sciences Publications | Projeto: | The Lundbeck Foundation (to JBS), the Novo Nordic Foundation (JBS), the Danish Medical Research Council (JBS and SH), and the European Research Council (ERC-ADG- 322966-DCVfusion, to MV). | Título da revista, periódico, livro ou evento: | eLife | Volume: | 6 | Resumo: | 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 | Direitos: | openAccess |
Aparece nas coleções: | 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 | Ver/Abrir |
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