Cargando…

STIM1L traps and gates Orai1 channels without remodeling the cortical ER

STIM proteins populate and expand cortical endoplasmic reticulum (ER) sheets to mediate store-operated Ca(2+) entry (SOCE) by trapping and gating Orai channels in ER-plasma membrane clusters. A longer splice variant, STIM1L, forms permanent ER-plasma membrane clusters and mediates rapid Ca(2+) influ...

Descripción completa

Detalles Bibliográficos
Autores principales: Saüc, Sophie, Bulla, Monica, Nunes, Paula, Orci, Lelio, Marchetti, Anna, Antigny, Fabrice, Bernheim, Laurent, Cosson, Pierre, Frieden, Maud, Demaurex, Nicolas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406124/
https://www.ncbi.nlm.nih.gov/pubmed/25736291
http://dx.doi.org/10.1242/jcs.164228
_version_ 1782367726054932480
author Saüc, Sophie
Bulla, Monica
Nunes, Paula
Orci, Lelio
Marchetti, Anna
Antigny, Fabrice
Bernheim, Laurent
Cosson, Pierre
Frieden, Maud
Demaurex, Nicolas
author_facet Saüc, Sophie
Bulla, Monica
Nunes, Paula
Orci, Lelio
Marchetti, Anna
Antigny, Fabrice
Bernheim, Laurent
Cosson, Pierre
Frieden, Maud
Demaurex, Nicolas
author_sort Saüc, Sophie
collection PubMed
description STIM proteins populate and expand cortical endoplasmic reticulum (ER) sheets to mediate store-operated Ca(2+) entry (SOCE) by trapping and gating Orai channels in ER-plasma membrane clusters. A longer splice variant, STIM1L, forms permanent ER-plasma membrane clusters and mediates rapid Ca(2+) influx in muscle. Here, we used electron microscopy, total internal reflection fluorescence (TIRF) microscopy and Ca(2+) imaging to establish the trafficking and signaling properties of the two STIM1 isoforms in Stim1(−/−)/Stim2(−/−) fibroblasts. Unlike STIM1, STIM1L was poorly recruited into ER-plasma membrane clusters and did not mediate store-dependent expansion of cortical ER cisternae. Removal of the STIM1 lysine-rich tail prevented store-dependent cluster enlargement, whereas inhibition of cytosolic Ca(2+) elevations or removal of the STIM1L actin-binding domain had no impact on cluster expansion. Finally, STIM1L restored robust but not accelerated SOCE and clustered with Orai1 channels more slowly than STIM1 following store depletion. These results indicate that STIM1L does not mediate rapid SOCE but can trap and gate Orai1 channels efficiently without remodeling cortical ER cisternae. The ability of STIM proteins to induce cortical ER formation is dispensable for SOCE and requires the lysine-rich tail of STIM1 involved in binding to phosphoinositides.
format Online
Article
Text
id pubmed-4406124
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher The Company of Biologists
record_format MEDLINE/PubMed
spelling pubmed-44061242016-04-15 STIM1L traps and gates Orai1 channels without remodeling the cortical ER Saüc, Sophie Bulla, Monica Nunes, Paula Orci, Lelio Marchetti, Anna Antigny, Fabrice Bernheim, Laurent Cosson, Pierre Frieden, Maud Demaurex, Nicolas J Cell Sci Research Article STIM proteins populate and expand cortical endoplasmic reticulum (ER) sheets to mediate store-operated Ca(2+) entry (SOCE) by trapping and gating Orai channels in ER-plasma membrane clusters. A longer splice variant, STIM1L, forms permanent ER-plasma membrane clusters and mediates rapid Ca(2+) influx in muscle. Here, we used electron microscopy, total internal reflection fluorescence (TIRF) microscopy and Ca(2+) imaging to establish the trafficking and signaling properties of the two STIM1 isoforms in Stim1(−/−)/Stim2(−/−) fibroblasts. Unlike STIM1, STIM1L was poorly recruited into ER-plasma membrane clusters and did not mediate store-dependent expansion of cortical ER cisternae. Removal of the STIM1 lysine-rich tail prevented store-dependent cluster enlargement, whereas inhibition of cytosolic Ca(2+) elevations or removal of the STIM1L actin-binding domain had no impact on cluster expansion. Finally, STIM1L restored robust but not accelerated SOCE and clustered with Orai1 channels more slowly than STIM1 following store depletion. These results indicate that STIM1L does not mediate rapid SOCE but can trap and gate Orai1 channels efficiently without remodeling cortical ER cisternae. The ability of STIM proteins to induce cortical ER formation is dispensable for SOCE and requires the lysine-rich tail of STIM1 involved in binding to phosphoinositides. The Company of Biologists 2015-04-15 /pmc/articles/PMC4406124/ /pubmed/25736291 http://dx.doi.org/10.1242/jcs.164228 Text en © 2015. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Saüc, Sophie
Bulla, Monica
Nunes, Paula
Orci, Lelio
Marchetti, Anna
Antigny, Fabrice
Bernheim, Laurent
Cosson, Pierre
Frieden, Maud
Demaurex, Nicolas
STIM1L traps and gates Orai1 channels without remodeling the cortical ER
title STIM1L traps and gates Orai1 channels without remodeling the cortical ER
title_full STIM1L traps and gates Orai1 channels without remodeling the cortical ER
title_fullStr STIM1L traps and gates Orai1 channels without remodeling the cortical ER
title_full_unstemmed STIM1L traps and gates Orai1 channels without remodeling the cortical ER
title_short STIM1L traps and gates Orai1 channels without remodeling the cortical ER
title_sort stim1l traps and gates orai1 channels without remodeling the cortical er
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406124/
https://www.ncbi.nlm.nih.gov/pubmed/25736291
http://dx.doi.org/10.1242/jcs.164228
work_keys_str_mv AT saucsophie stim1ltrapsandgatesorai1channelswithoutremodelingthecorticaler
AT bullamonica stim1ltrapsandgatesorai1channelswithoutremodelingthecorticaler
AT nunespaula stim1ltrapsandgatesorai1channelswithoutremodelingthecorticaler
AT orcilelio stim1ltrapsandgatesorai1channelswithoutremodelingthecorticaler
AT marchettianna stim1ltrapsandgatesorai1channelswithoutremodelingthecorticaler
AT antignyfabrice stim1ltrapsandgatesorai1channelswithoutremodelingthecorticaler
AT bernheimlaurent stim1ltrapsandgatesorai1channelswithoutremodelingthecorticaler
AT cossonpierre stim1ltrapsandgatesorai1channelswithoutremodelingthecorticaler
AT friedenmaud stim1ltrapsandgatesorai1channelswithoutremodelingthecorticaler
AT demaurexnicolas stim1ltrapsandgatesorai1channelswithoutremodelingthecorticaler