STIM1L is a new actin-binding splice variant involved in fast repetitive Ca 2+ release

Abstract

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. © 2011 Darbellay etal.