Mutations that disrupt Ca²⁺-binding activity endow Doc2β with novel functional properties during synaptic transmission.

ABSTRACT: Double C2-domain protein (Doc2) is a Ca(2+)-binding protein implicated in asynchronous and spontaneous neurotransmitter release. Here we demonstrate that each of its C2 domains senses Ca(2+); moreover, the tethered tandem C2 domains display properties distinct from the isolated domains. We confirm that overexpression of a mutant form of Doc2β, in which two acidic Ca(2+) ligands in the C2A domain and two in the C2B domain have been neutralized, results in markedly enhanced asynchronous release in synaptotagmin 1-knockout neurons. Unlike wild-type (wt) Doc2β, which translocates to the plasma membrane in response to increases in [Ca(2+)](i), the quadruple Ca(2+)-ligand mutant does not bind Ca(2+) but is constitutively associated with the plasma membrane; this effect is due to substitution of

SUBMITTER: Gaffaney JD 

PROVIDER: S-EPMC3923640 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature