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

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

SUBMITTER: Houy S 

PROVIDER: S-EPMC5758110 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature