Premium
Peripheral Coupling Sites Formed by STIM1 Govern the Contractility of Vascular Smooth Muscle Cells
Author(s) -
Krishnan Vivek,
Ali Sher,
Gonzales Albert,
Thakore Pratish,
Griffin Caoimhin,
Yamasaki Evan,
Alvarado Michael G.,
Johnson Martin T.,
Trebak Mohamed,
Earley Scott
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.r5019
Subject(s) - stim1 , endoplasmic reticulum , vascular smooth muscle , microbiology and biotechnology , contractility , colocalization , orai1 , chemistry , biology , medicine , endocrinology , biophysics , smooth muscle
Peripheral coupling between the sarcoplasmic reticulum (SR) and plasma membrane (PM) forms signaling complexes that regulate the membrane potential and contractility of vascular smooth muscle cells (VSMCs). However, the mechanisms responsible for these membrane interactions are poorly understood. In many cells, STIM1 (stromal‐interaction molecule 1), a single transmembrane‐domain protein that resides in the endoplasmic reticulum (ER), transiently moves to ER‐PM junctions in response to depletion of ER Ca 2+ stores and initiates store‐operated Ca 2+ entry (SOCE). Fully differentiated VSMCs express STIM1 but exhibit only marginal SOCE activity. We hypothesized that STIM1 is constitutively active in contractile VSMCs and maintains peripheral coupling. In support of this concept, we found that the number and size of SR‐PM interacting sites were decreased and SR‐dependent Ca 2+ signaling processes were disrupted in freshly isolated cerebral artery SMCs from tamoxifen‐inducible, SMC‐specific STIM1‐knockout ( Stim1‐ smKO) mice. VSMCs from Stim1‐ smKO mice also exhibited a reduction in nanoscale colocalization between Ca 2+ ‐release sites on the SR and Ca 2+ ‐activated ion channels on the PM, accompanied by diminished channel activity. Stim1‐ smKO mice were hypotensive and resistance arteries isolated from them displayed blunted contractility. These data suggest that STIM1 – independent of SR Ca 2+ store depletion – is critically important for stable peripheral coupling in contractile VSMCs.