MARCH9-mediated Ubiquitination Regulates MHC I Export from the TGN

Overview

Journal Immunol Cell Biol

Publisher Wiley

Specialties Allergy & Immunology
Cell Biology

Date 2017 Jun 1

PMID 28559542

Citations 23

Authors

Francesca De Angelis Rigotti

Aude de Gassart

Carina Pforr

Florencia Cano

Prudence Nguessan

Alexis Combes

Voahirana Camossetto

Paul J Lehner

Philippe Pierre

Evelina Gatti

Affiliations

Soon will be listed here.

Abstract

Given the heterogeneous nature of antigens, major histocompatibility complex class I (MHC I) intracellular transport intersects with multiple degradation pathways for efficient peptide loading and presentation to cytotoxic T cells. MHC I loading with peptides in the endoplasmic reticulum (ER) is a tightly regulated process, while post-ER intracellular transport is considered to occur by default, leading to peptide-bearing MHC I delivery to the plasma membrane. We show here that MHC I traffic is submitted to a previously uncharacterized sorting step at the trans Golgi network (TGN), dependent on the ubiquitination of its cytoplasmic tail lysine residues. MHC I ubiquitination is mediated by the E3 ligase membrane-associated RING-CH 9 (MARCH9) and allows MHC I access to Syntaxin 6-positive endosomal compartments. We further show that MARCH9 can also target the human MHC I-like lipid antigen-presentation molecule CD1a. MARCH9 expression is modulated by microbial pattern exposure in dendritic cells (DCs), thus revealing the role of this ubiquitin E3 ligase in coordinating MHC I access to endosomes and DC activation for efficient antigen cross-presentation.

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