Phosphorylation of STIM1 at ERK/CDK sites is dispensable for cell migration and ER partitioning in mitosis. (December 2021)

• Record Type: Journal Article
• Authors: Hammad, Ayat S.; Yu, Fang; Botheju, Welathanthrige S.; Elmi, Asha; Alcantara-Adap, Ethel; Machaca, Khaled
• Is Part Of: Cell calcium. Volume 100(2021)
• Publication Date: 2021-12
• Subjects: Store-operated calcium entry -- Mitosis -- Endoplasmic reticulum -- Cell migration -- Calcium Signaling -- STIM1; Calcium -- Metabolism -- Periodicals; Vertebrates -- Physiology -- Periodicals; Calcium -- Physiological effect -- Periodicals; Cell physiology -- Periodicals; Calcium in the body -- Periodicals; 572.516
• DOI: 10.1016/j.ceca.2021.102496
• Languages: English
• ISSNs: 0143-4160

Abstract

Highlights: STIM1 phosphorylation is not involved in ER partitioning during mitosis. STIM1 phosphorylation does not play a major role in cell migration. STIM1 phosphorylation is not required for SOCE activation. Abstract: Store-operated Ca 2+ entry (SOCE) is a ubiquitous Ca 2+ influx pathway required for multiple physiological functions including cell motility. SOCE is triggered in response to depletion of intracellular Ca 2+ stores following the activation of the endoplasmic reticulum (ER) Ca 2+ sensor STIM1, which recruits the plasma membrane (PM) Ca 2+ channel Orai1 at ER-PM junctions. STIM1 is phosphorylated dynamically, and this phosphorylation has been implicated in several processes including SOCE inactivation during M-phase, maximal SOCE activation, ER segregation during mitosis, and cell migration. Human STIM1 has 10 Ser/Thr residues in its cytosolic domain that match the ERK/CDK consensus phosphorylation. We recently generated a mouse knock-in line where wild-type STIM1 was replaced by a non-phosphorylatable STIM1 with all ten S/Ts mutated to Ala (STIM1–10A). Here, we generate mouse embryonic fibroblasts (MEF) from the STIM1–10A mouse line and a control MEF line (WT) that express wild-type STIM1 from a congenic mouse strain. These lines offer a unique model to address the role of STIM1 phosphorylation at endogenous expression levels in contrast to previous studies that relied mostly on overexpression. We show that STIM1 phosphorylation at ERK/CDK sites is not required for SOCE activation, cell migration, or ER partitioning during mitosis. These results rule out STIM1 phosphorylation as a regulator of SOCE, migration, and ER distribution in mitosis. Graphical abstract: Image, graphical abstract