UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells.
- Maschalidi S INSERM UMR1163, Laboratory of Normal and Pathological Homeostasis of the Immune System, Imagine Institute, 75015, Paris, France.
- Nunes-Hasler P Department of Cell Physiology and Metabolism, University of Geneva, CH-1211, Geneva, Switzerland.
- Nascimento CR Faculté de médecine Paris Descartes, Université Paris Descartes, 75015, Paris, France.
- Sallent I Faculté de médecine Paris Descartes, Université Paris Descartes, 75015, Paris, France.
- Lannoy V Faculté de médecine Paris Descartes, Université Paris Descartes, 75015, Paris, France.
- Garfa-Traore M Faculté de médecine Paris Descartes, Université Paris Descartes, 75015, Paris, France.
- Cagnard N Faculté de médecine Paris Descartes, Université Paris Descartes, 75015, Paris, France.
- Sepulveda FE INSERM UMR1163, Laboratory of Normal and Pathological Homeostasis of the Immune System, Imagine Institute, 75015, Paris, France.
- Vargas P Institut Curie, PSL Research University, Centre National de la Recherche Scientifique, UMR 144, 75005, Paris, France.
- Lennon-Duménil AM Institut National de la Santé et de la Recherché Médicale, Unité 932, Institut Curie, PSL Research University, 75005, Paris, France.
- van Endert P Faculté de médecine Paris Descartes, Université Paris Descartes, 75015, Paris, France.
- Capiod T Faculté de médecine Paris Descartes, Université Paris Descartes, 75015, Paris, France.
- Demaurex N Department of Cell Physiology and Metabolism, University of Geneva, CH-1211, Geneva, Switzerland.
- Darrasse-Jèze G Faculté de médecine Paris Descartes, Université Paris Descartes, 75015, Paris, France.
- Manoury B Faculté de médecine Paris Descartes, Université Paris Descartes, 75015, Paris, France. benedicte.manoury@inserm.fr.
- 2017-11-22
Published in:
- Nature communications. - 2017
Animals
Antigen Presentation
Antigens
Calcium
Cells, Cultured
Cross-Priming
Dendritic Cells
Endoplasmic Reticulum
Female
Humans
Male
Membrane Transport Proteins
Mice
Mice, Inbred C57BL
Protein Binding
Stromal Interaction Molecule 1
English
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-Ca2+-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.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1038/s41467-017-01601-5
- PMID 29158474
- Persistent URL
- https://sonar.ch/global/documents/232615
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