Functional analysis of the interface between the tandem C2 domains of synaptotagmin-1.

Journal Article (Journal Article)

C2 domains are widespread motifs that often serve as Ca(2+)-binding modules; some proteins have more than one copy. An open issue is whether these domains, when duplicated within the same parent protein, interact with one another to regulate function. In the present study, we address the functional significance of interfacial residues between the tandem C2 domains of synaptotagmin (syt)-1, a Ca(2+) sensor for neuronal exocytosis. Substitution of four residues, YHRD, at the domain interface, disrupted the interaction between the tandem C2 domains, altered the intrinsic affinity of syt-1 for Ca(2+), and shifted the Ca(2+) dependency for binding to membranes and driving membrane fusion in vitro. When expressed in syt-1 knockout neurons, the YHRD mutant yielded reductions in synaptic transmission, as compared with the wild-type protein. These results indicate that physical interactions between the tandem C2 domains of syt-1 contribute to excitation-secretion coupling.

Full Text

Duke Authors

Cited Authors

  • Evans, CS; He, Z; Bai, H; Lou, X; Jeggle, P; Sutton, RB; Edwardson, JM; Chapman, ER

Published Date

  • March 15, 2016

Published In

Volume / Issue

  • 27 / 6

Start / End Page

  • 979 - 989

PubMed ID

  • 26792839

Pubmed Central ID

  • PMC4791141

Electronic International Standard Serial Number (EISSN)

  • 1939-4586

Digital Object Identifier (DOI)

  • 10.1091/mbc.E15-07-0503


  • eng

Conference Location

  • United States