1. Calcium-stimulated disassembly of focal adhesions mediated by an ORP3/IQSec1 complex
- Author
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Ryan S D'Souza, Jun Y Lim, Alper Turgut, Kelly Servage, Junmei Zhang, Kim Orth, Nisha G Sosale, Matthew J Lazzara, Jeremy Allegood, and James E Casanova
- Subjects
GTPase ,ORP ,IQSec1 ,cell migration ,cell adhesion ,lipid transfer ,Medicine ,Science ,Biology (General) ,QH301-705.5 - 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 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.
- Published
- 2020
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