UNC93B1 Interacts with the Calcium Sensor STIM1 for Efficient Antigen Cross-presentation in Dendritic Cells

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Nov 22

PMID 29158474

Citations 21

Authors

Sophia Maschalidi

Paula Nunes-Hasler

Clarissa R Nascimento

Ignacio Sallent

Valerie Lannoy

Meriem Garfa-Traore

Nicolas Cagnard

Fernando E Sepulveda

Pablo Vargas

Ana-Maria Lennon-Dumenil

Peter van Endert

Thierry Capiod

Nicolas Demaurex

Guillaume Darrasse-Jeze

Benedicte Manoury

Affiliations

Soon will be listed here.

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-Ca-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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