Article open access publication

Doc2B acts as a calcium sensor for vesicle priming requiring synaptotagmin-1, Munc13-2 and SNAREs

eLife, eLife, ISSN 2050-084X

Volume 6, 2017

DOI:10.7554/elife.27000, Dimensions: pub.1099932185, PMC: PMC5758110, PMID: 29274147,



  1. (1) University of Copenhagen, grid.5254.6, KU
  2. (2) VU University Medical Center, grid.16872.3a
  3. (3) Discovery Sciences, Innovative Medicines and Early Development, AstraZeneca R&D, Cambridge, United Kingdom.
  4. (4) VU Amsterdam, grid.12380.38







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.


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