STIM1L is a new actin-binding splice variant involved in fast repetitive Ca2+ release

• Published in: The Journal of cell biology Vol. 194; no. 2; pp. 335 - 346
• Main Authors: Darbellay, Basile, Arnaudeau, Serge, Bader, Charles R, Konig, Stephane, Bernheim, Laurent
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 25.07.2011
• Subjects: Actins - metabolism; Alternative Splicing - genetics; Animals; Calcium - metabolism; Calcium Channels - metabolism; Cells, Cultured; Exons - genetics; Humans; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; ORAI1 Protein; Protein Isoforms - genetics; Protein Isoforms - metabolism; Signal Transduction; Stromal Interaction Molecule 1
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201012157

Cytosolic Ca(2+) signals encoded by repetitive Ca(2+) releases rely on two processes to refill Ca(2+) stores: Ca(2+) reuptake from the cytosol and activation of a Ca(2+) influx via store-operated Ca(2+) entry (SOCE). However, SOCE activation is a slow process. It is delayed by >30 s after store depletion because stromal interaction molecule 1 (STIM1), the Ca(2+) sensor of the intracellular stores, must form clusters and migrate to the membrane before being able to open Orai1, the plasma membrane Ca(2+) channel. In this paper, we identify a new protein, STIM1L, that colocalizes with Orai1 Ca(2+) channels and interacts with actin to form permanent clusters. This property allowed the immediate activation of SOCE, a characteristic required for generating repetitive Ca(2+) signals with frequencies within seconds such as those frequently observed in excitable cells. STIM1L was expressed in several mammalian tissues, suggesting that many cell types rely on this Ca(2+) sensor for their Ca(2+) homeostasis and intracellular signaling.