S-acylation of Orai1 regulates store-operated Ca2+ entry

Savannah J. West, Goutham Kodakandla, Qioachu Wang, Ritika Tewari, Michael X. Zhu, Darren Boehning, Askar M. Akimzhanov

Research output: Contribution to journalArticlepeer-review

Abstract

Store-operated Ca2+ entry is a central component of intracellular Ca2+ signaling pathways. The Ca2+ release-activated channel (CRAC) mediates store-operated Ca2+ entry in many different cell types. The CRAC channel is composed of the plasma membrane (PM)-localized Orai1 channel and endoplasmic reticulum (ER)-localized STIM1 Ca2+ sensor. Upon ER Ca2+ store depletion, Orai1 and STIM1 form complexes at ER-PM junctions, leading to the formation of activated CRAC channels. Although the importance of CRAC channels is well described, the underlying mechanisms that regulate the recruitment of Orai1 to ER-PM junctions are not fully understood. Here, we describe the rapid and transient S-acylation of Orai1. Using biochemical approaches, we show that Orai1 is rapidly S-acylated at cysteine 143 upon ER Ca2+ store depletion. Importantly, S-acylation of cysteine 143 is required for Orai1-mediated Ca2+ entry and recruitment to STIM1 puncta. We conclude that store depletion-induced S-acylation of Orai1 is necessary for recruitment to ER-PM junctions, subsequent binding to STIM1 and channel activation.

Original languageEnglish (US)
JournalJournal of cell science
Volume135
Issue number5
DOIs
StatePublished - Mar 1 2022

All Science Journal Classification (ASJC) codes

  • Cell Biology

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