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

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 chann...

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Bibliographic Details
Published inbioRxiv
Main Authors Casanova, James E, D'souza, Ryan S, Lim, Jun Y, Servage, Kelly, Zhang, Junmei, Orth, Kim, Sosale, Nisha, Lazzara, Matthew, Allegood, Jeremy
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 05.12.2019
Subjects
Calcium channels
Calcium influx
Cell adhesion & migration
Cell migration
Guanosine triphosphatases
Lecithin
Orai1 protein
Phosphatidylcholine
STIM1 protein
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Summary: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 contact sites adjacent to FAs. In addition to allosterically activating IQSec1, ORP3 also extracts PI4P from the PM, in exchange for phosphatidylcholine. ORP3-mediated lipid exchange is also important for FA turnover. Together, these findings identify a new pathway that links calcium influx to FA turnover during cell migration.
DOI:10.1101/866392