Localized phosphoinositide metabolism regulates STIM1/ORAI1 fast inactivation
entry. MTMR7 alters plasma membrane PI(3,5)P2 and PI(4,5)P2 levels, increasing ORAI1 inactivation and decreasing SOCE. Loss of catalytic phosphatase function of MTMR7 weakens ORAI1 inactivation and enhances SOCE activity, while the disruption of MTMR7 and STIM1 association retains ORAI1 inactivation. The MTMR7/STIM1 complex positions MTMR7 at ER-plasma membrane contact sites to fine-tune lipid signaling, prevent premature STIM1 activation, and modify ORAI1 inactivation. These findings provide insight into novel modes of regulation of ORAI1 inactivation by phosphoinositides (PIPs).
Authors
- Harley T. Kurata (ORCID: https://orcid.org/0000-0003-4357-4189)
- Marek Michalak (ORCID: https://orcid.org/0000-0002-9343-9084)
- Jody Groenendyk
- Shawn M. Lamothe (ORCID: https://orcid.org/0000-0001-8722-2631)
- Nicolas Touret (ORCID: https://orcid.org/0000-0003-3700-6302)
- Ning Dai
Institutions
- University of Alberta (CA)
Publication Details
- Journal
- iScience
- Published
- 2026-03-31
- DOI
- https://doi.org/10.1016/j.isci.2026.115543
- Primary Topic
- Ion Channels and Receptors
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- University of Alberta
- University Hospital Foundation
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada