Translocation between PI(4,5)P2-poor and PI(4,5)P2-rich microdomains during store depletion determines STIM1 conformation and Orai1 gating

Translocation between PI(4,5)P2-poor and PI(4,5)P2-rich microdomains during store depletion determines STIM1 conformation and Orai1 gating

The Orai1-STIM1 current undergoes slow Ca2+-dependent inactivation (SCDI) mediated by binding of SARAF to STIM1. Here, we report the use of SCDI by SARAF as a probe of the conformation and microdomain localization of the Orai1-STIM1 complex. We find that interaction of STIM1 with Orai1 C terminus an...

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Main Authors: Maléth, Jozsef, Choi, Seok, Muallem, Shmuel, Ahuja, Malini
Format: Online
Language:English
Published: 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270102/
id pubmed-4270102
recordtype oai_dc
spelling pubmed-42701022015-06-17 Translocation between PI(4,5)P2-poor and PI(4,5)P2-rich microdomains during store depletion determines STIM1 conformation and Orai1 gating Maléth, Jozsef Choi, Seok Muallem, Shmuel Ahuja, Malini Article The Orai1-STIM1 current undergoes slow Ca2+-dependent inactivation (SCDI) mediated by binding of SARAF to STIM1. Here, we report the use of SCDI by SARAF as a probe of the conformation and microdomain localization of the Orai1-STIM1 complex. We find that interaction of STIM1 with Orai1 C terminus and the STIM1 K-domain are required for interaction of SARAF with STIM1 and SCDI. STIM1-Orai1 must be in a PM/ER microdomain tethered by E-Syt1, stabilized by Septin4 and enriched in PI(4,5)P2 for STIM1-SARAF interaction. Targeting STIM1 to PI(4,5)P2 rich and poor microdomains reveals that SARAF-dependent SCDI is observed only when STIM1-Orai1 are within the PI(4,5)P2-rich microdomain. Notably, store depletion results in transient localization of STIM1-Orai1 in the PI(4,5)P2-poor microdomain, which then translocate to the PI(4,5)P2-rich domain. These findings reveal the role of PM/ER tethers in the regulation of Orai1 function and a new mode of regulation by PI(4,5)P2 involving translocation between PI(4,5)P2 microdomains. 2014-12-17 /pmc/articles/PMC4270102/ /pubmed/25517631 http://dx.doi.org/10.1038/ncomms6843 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Maléth, Jozsef
Choi, Seok
Muallem, Shmuel
Ahuja, Malini
spellingShingle Maléth, Jozsef
Choi, Seok
Muallem, Shmuel
Ahuja, Malini
Translocation between PI(4,5)P2-poor and PI(4,5)P2-rich microdomains during store depletion determines STIM1 conformation and Orai1 gating
author_facet Maléth, Jozsef
Choi, Seok
Muallem, Shmuel
Ahuja, Malini
author_sort Maléth, Jozsef
title Translocation between PI(4,5)P2-poor and PI(4,5)P2-rich microdomains during store depletion determines STIM1 conformation and Orai1 gating
title_short Translocation between PI(4,5)P2-poor and PI(4,5)P2-rich microdomains during store depletion determines STIM1 conformation and Orai1 gating
title_full Translocation between PI(4,5)P2-poor and PI(4,5)P2-rich microdomains during store depletion determines STIM1 conformation and Orai1 gating
title_fullStr Translocation between PI(4,5)P2-poor and PI(4,5)P2-rich microdomains during store depletion determines STIM1 conformation and Orai1 gating
title_full_unstemmed Translocation between PI(4,5)P2-poor and PI(4,5)P2-rich microdomains during store depletion determines STIM1 conformation and Orai1 gating
title_sort translocation between pi(4,5)p2-poor and pi(4,5)p2-rich microdomains during store depletion determines stim1 conformation and orai1 gating
description The Orai1-STIM1 current undergoes slow Ca2+-dependent inactivation (SCDI) mediated by binding of SARAF to STIM1. Here, we report the use of SCDI by SARAF as a probe of the conformation and microdomain localization of the Orai1-STIM1 complex. We find that interaction of STIM1 with Orai1 C terminus and the STIM1 K-domain are required for interaction of SARAF with STIM1 and SCDI. STIM1-Orai1 must be in a PM/ER microdomain tethered by E-Syt1, stabilized by Septin4 and enriched in PI(4,5)P2 for STIM1-SARAF interaction. Targeting STIM1 to PI(4,5)P2 rich and poor microdomains reveals that SARAF-dependent SCDI is observed only when STIM1-Orai1 are within the PI(4,5)P2-rich microdomain. Notably, store depletion results in transient localization of STIM1-Orai1 in the PI(4,5)P2-poor microdomain, which then translocate to the PI(4,5)P2-rich domain. These findings reveal the role of PM/ER tethers in the regulation of Orai1 function and a new mode of regulation by PI(4,5)P2 involving translocation between PI(4,5)P2 microdomains.
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270102/
_version_ 1613168667516731392

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