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UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells

Dendritic cells (DC) have the unique ability to present exogenous antigens via the major histocompatibility complex class I pathway to stimulate naive CD8(+) T cells. In DCs with a non-functional mutation in Unc93b1 (3d mutation), endosomal acidification, phagosomal maturation, antigen degradation,...

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Autores principales: Maschalidi, Sophia, Nunes-Hasler, Paula, Nascimento, Clarissa R, Sallent, Ignacio, Lannoy, Valérie, Garfa-Traore, Meriem, Cagnard, Nicolas, Sepulveda, Fernando E., Vargas, Pablo, Lennon-Duménil, Ana-Maria, van Endert, Peter, Capiod, Thierry, Demaurex, Nicolas, Darrasse-Jèze, Guillaume, Manoury, Bénédicte
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696382/
https://www.ncbi.nlm.nih.gov/pubmed/29158474
http://dx.doi.org/10.1038/s41467-017-01601-5
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author Maschalidi, Sophia
Nunes-Hasler, Paula
Nascimento, Clarissa R
Sallent, Ignacio
Lannoy, Valérie
Garfa-Traore, Meriem
Cagnard, Nicolas
Sepulveda, Fernando E.
Vargas, Pablo
Lennon-Duménil, Ana-Maria
van Endert, Peter
Capiod, Thierry
Demaurex, Nicolas
Darrasse-Jèze, Guillaume
Manoury, Bénédicte
author_facet Maschalidi, Sophia
Nunes-Hasler, Paula
Nascimento, Clarissa R
Sallent, Ignacio
Lannoy, Valérie
Garfa-Traore, Meriem
Cagnard, Nicolas
Sepulveda, Fernando E.
Vargas, Pablo
Lennon-Duménil, Ana-Maria
van Endert, Peter
Capiod, Thierry
Demaurex, Nicolas
Darrasse-Jèze, Guillaume
Manoury, Bénédicte
author_sort Maschalidi, Sophia
collection PubMed
description Dendritic cells (DC) have the unique ability to present exogenous antigens via the major histocompatibility complex class I pathway to stimulate naive CD8(+) T cells. In DCs with a non-functional mutation in Unc93b1 (3d mutation), endosomal acidification, phagosomal maturation, antigen degradation, antigen export to the cytosol and the function of the store-operated-Ca(2+)-entry regulator STIM1 are impaired. These defects result in compromised antigen cross-presentation and anti-tumor responses in 3d-mutated mice. Here, we show that UNC93B1 interacts with the calcium sensor STIM1 in the endoplasmic reticulum, a critical step for STIM1 oligomerization and activation. Expression of a constitutively active STIM1 mutant, which no longer binds UNC93B1, restores antigen degradation and cross-presentation in 3d-mutated DCs. Furthermore, ablation of STIM1 in mouse and human cells leads to a decrease in cross-presentation. Our data indicate that the UNC93B1 and STIM1 cooperation is important for calcium flux and antigen cross-presentation in DCs.
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spelling pubmed-56963822017-11-22 UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells Maschalidi, Sophia Nunes-Hasler, Paula Nascimento, Clarissa R Sallent, Ignacio Lannoy, Valérie Garfa-Traore, Meriem Cagnard, Nicolas Sepulveda, Fernando E. Vargas, Pablo Lennon-Duménil, Ana-Maria van Endert, Peter Capiod, Thierry Demaurex, Nicolas Darrasse-Jèze, Guillaume Manoury, Bénédicte Nat Commun Article Dendritic cells (DC) have the unique ability to present exogenous antigens via the major histocompatibility complex class I pathway to stimulate naive CD8(+) T cells. In DCs with a non-functional mutation in Unc93b1 (3d mutation), endosomal acidification, phagosomal maturation, antigen degradation, antigen export to the cytosol and the function of the store-operated-Ca(2+)-entry regulator STIM1 are impaired. These defects result in compromised antigen cross-presentation and anti-tumor responses in 3d-mutated mice. Here, we show that UNC93B1 interacts with the calcium sensor STIM1 in the endoplasmic reticulum, a critical step for STIM1 oligomerization and activation. Expression of a constitutively active STIM1 mutant, which no longer binds UNC93B1, restores antigen degradation and cross-presentation in 3d-mutated DCs. Furthermore, ablation of STIM1 in mouse and human cells leads to a decrease in cross-presentation. Our data indicate that the UNC93B1 and STIM1 cooperation is important for calcium flux and antigen cross-presentation in DCs. Nature Publishing Group UK 2017-11-21 /pmc/articles/PMC5696382/ /pubmed/29158474 http://dx.doi.org/10.1038/s41467-017-01601-5 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Maschalidi, Sophia
Nunes-Hasler, Paula
Nascimento, Clarissa R
Sallent, Ignacio
Lannoy, Valérie
Garfa-Traore, Meriem
Cagnard, Nicolas
Sepulveda, Fernando E.
Vargas, Pablo
Lennon-Duménil, Ana-Maria
van Endert, Peter
Capiod, Thierry
Demaurex, Nicolas
Darrasse-Jèze, Guillaume
Manoury, Bénédicte
UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells
title UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells
title_full UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells
title_fullStr UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells
title_full_unstemmed UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells
title_short UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells
title_sort unc93b1 interacts with the calcium sensor stim1 for efficient antigen cross-presentation in dendritic cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696382/
https://www.ncbi.nlm.nih.gov/pubmed/29158474
http://dx.doi.org/10.1038/s41467-017-01601-5
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