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

Maschalidi, Sophia
Nascimento, Clarissa R
Sallent, Ignacio
Lannoy, Valérie
Garfa-Traore, Meriem
Cagnard, Nicolas
Sepulveda, Fernando E
show hidden authors show all authors [1 - 15]
Published in Nature communications. 2017, vol. 8, no. 1, 1640
Abstract 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.
Keywords Calcium signalingDendritic cellsImmunityPhagocytosis
PMID: 29158474
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Article (Published version) (3.1 MB) - public document Free access
Research groups Mécanismes de la présentation croisée des antigènes (1011)
Signaux intracellulaires (210)
Swiss National Science Foundation: 31003A_149566
Swiss National Science Foundation: CRSII3_160782
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MASCHALIDI, Sophia et al. UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells. In: Nature Communications, 2017, vol. 8, n° 1, p. 1640. doi: 10.1038/s41467-017-01601-5 https://archive-ouverte.unige.ch/unige:100198

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Deposited on : 2017-12-12

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