TY - JOUR TI - Calcium-stimulated disassembly of focal adhesions mediated by an ORP3/IQSec1 complex AU - D'Souza, Ryan S AU - Lim, Jun Y AU - Turgut, Alper AU - Servage, Kelly AU - Zhang, Junmei AU - Orth, Kim AU - Sosale, Nisha G AU - Lazzara, Matthew J AU - Allegood, Jeremy AU - Casanova, James E A2 - Parsons, Maddy A2 - Akhmanova, Anna VL - 9 PY - 2020 DA - 2020/04/01 SP - e54113 C1 - eLife 2020;9:e54113 DO - 10.7554/eLife.54113 UR - https://doi.org/10.7554/eLife.54113 AB - 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. KW - GTPase KW - ORP KW - IQSec1 KW - cell migration KW - cell adhesion KW - lipid transfer JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -