Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/108139
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Houy, Sébastien | - |
dc.contributor.author | Groffen, Alexander J | - |
dc.contributor.author | Ziomkiewicz, Iwona | - |
dc.contributor.author | Verhage, Matthijs | - |
dc.contributor.author | Pinheiro, Paulo S. | - |
dc.contributor.author | Sørensen, Jakob Balslev | - |
dc.date.accessioned | 2023-08-12T18:29:19Z | - |
dc.date.available | 2023-08-12T18:29:19Z | - |
dc.date.issued | 2017-12-23 | - |
dc.identifier.issn | 2050-084X | pt |
dc.identifier.uri | https://hdl.handle.net/10316/108139 | - |
dc.description.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. | pt |
dc.language.iso | eng | pt |
dc.publisher | eLife Sciences Publications | pt |
dc.relation | 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). | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject | adrenaline; capacitance measurements; chromaffin cell; exocytosis; membrane fusion; mouse; neuroscience | pt |
dc.subject.mesh | Animals | pt |
dc.subject.mesh | Calcium | pt |
dc.subject.mesh | Calcium-Binding Proteins | pt |
dc.subject.mesh | Cells, Cultured | pt |
dc.subject.mesh | Chromaffin Cells | pt |
dc.subject.mesh | Gene Expression | pt |
dc.subject.mesh | Gene Knockout Techniques | pt |
dc.subject.mesh | Intracellular Signaling Peptides and Proteins | pt |
dc.subject.mesh | Mice | pt |
dc.subject.mesh | Mice, Knockout | pt |
dc.subject.mesh | Nerve Tissue Proteins | pt |
dc.subject.mesh | SNARE Proteins | pt |
dc.subject.mesh | Secretory Vesicles | pt |
dc.subject.mesh | Synaptotagmin I | pt |
dc.title | Doc2B acts as a calcium sensor for vesicle priming requiring synaptotagmin-1, Munc13-2 and SNAREs | pt |
dc.type | article | - |
degois.publication.firstPage | e27000 | pt |
degois.publication.title | eLife | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.7554/eLife.27000 | pt |
degois.publication.volume | 6 | pt |
dc.date.embargo | 2017-12-23 | * |
uc.date.periodoEmbargo | 0 | pt |
item.openairetype | article | - |
item.fulltext | Com Texto completo | - |
item.languageiso639-1 | en | - |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0002-9024-1021 | - |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
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File | Description | Size | Format | |
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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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This item is licensed under a Creative Commons License