Calmodulin dissociates the STIM1-Orai1 complex and STIM1 oligomers.

Li, Xin; Wu, Guangyan; Yang, Yin; Fu, Shijuan; Liu, Xiaofen; Kang, Huimin; Yang, Xue; Su, Xun-Cheng et al. · Nat Commun · 2017

basic_science · Level V

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Abstract

Store-operated calcium entry (SOCE) is a major pathway for calcium ions influx into cells and has a critical role in various cell functions. Here we demonstrate that calcium-bound calmodulin (Ca<sup>2+</sup>-CaM) binds to the core region of activated STIM1. This interaction facilitates slow Ca<sup>2+</sup>-dependent inactivation after Orai1 channel activation by wild-type STIM1 or a constitutively active STIM1 mutant. We define the CaM-binding site in STIM1, which is adjacent to the STIM1-Orai1 coupling region. The binding of Ca<sup>2+</sup>-CaM to activated STIM1 disrupts the STIM1-Orai1 complex and also disassembles STIM1 oligomer. Based on these results we propose a model for the calcium-bound CaM-regulated deactivation of SOCE.

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