Calcium-stimulated disassembly of focal adhesions mediated by an orp3/iqsec1 complex

Ryan S. D’souza, Jun Y. Lim, Alper Turgut, Kelly Servage, Junmei Zhang, Kim Orth, Nisha G. Sosale, Matthew J. Lazzara, Jeremy Allegood, James E. Casanova

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish (US)
Article numbere54113
JournaleLife
Volume9
DOIs
StatePublished - Apr 2020

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    D’souza, R. S., Lim, J. Y., Turgut, A., Servage, K., Zhang, J., Orth, K., Sosale, N. G., Lazzara, M. J., Allegood, J., & Casanova, J. E. (2020). Calcium-stimulated disassembly of focal adhesions mediated by an orp3/iqsec1 complex. eLife, 9, [e54113]. https://doi.org/10.7554/eLife.54113