Calcium-stimulated disassembly of focal adhesions mediated by an ORP3/IQSec1 complex.

ABSTRACT: Coordinated assembly and disassembly of integrin-mediated focal adhesions (FAs) is essential for cell migration. Many studies have shown that FA disassembly requires Ca²⁺ influx, however our understanding of this process remains incomplete. Here, we show that Ca²⁺ influx via STIM1/Orai1 calcium channels, which cluster near FAs, leads to activation of the GTPase Arf5 via the Ca²⁺-activated GEF IQSec1, and that both IQSec1 and Arf5 activation are essential for adhesion disassembly. We further show that IQSec1 forms a complex with the lipid transfer protein ORP3, and that Ca²⁺ influx triggers PKC-dependent translocation of this complex to ER/plasma membrane (PM) contact sites adjacent to FAs. In addition to allosterically activating IQSec1, ORP3 als

SUBMITTER: D'Souza RS 

PROVIDER: S-EPMC7159923 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature