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

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.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

West SJ,Kodakandla G,Wang Q,Tewari R,Zhu MX,Boehning D,Akimzhanov AM

doi

10.1242/jcs.258579

keywords:

["Ca2+ channel","Calcium","Orai1","Palmitoylation","S-acylation"]

subject

Has Abstract

pub_date

2022-03-01 00:00:00

issue

5

eissn

0021-9533

issn

1477-9137

pii

269207

journal_volume

135

pub_type

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