Affordable Access

deepdyve-link
Publisher Website

MARCH1 protects the lipid raft and tetraspanin web from MHCII proteotoxicity in dendritic cells.

Authors
  • Oh, Jaehak1, 2
  • Perry, Justin S A3
  • Pua, Heather2, 3
  • Irgens-Möller, Nicole1, 2
  • Ishido, Satoshi4
  • Hsieh, Chyi-Song5
  • Shin, Jeoung-Sook6, 2
  • 1 Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA.
  • 2 Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA.
  • 3 Department of Pathology, University of California, San Francisco, San Francisco, CA.
  • 4 Department of Microbiology, Hyogo College of Medicine 1-1, Mukogawa-cho, Nishinomiya, Japan. , (Japan)
  • 5 Department of Internal Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, MO.
  • 6 Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA [email protected]
Type
Published Article
Journal
The Journal of Cell Biology
Publisher
The Rockefeller University Press
Publication Date
Apr 02, 2018
Volume
217
Issue
4
Pages
1395–1410
Identifiers
DOI: 10.1083/jcb.201611141
PMID: 29371232
Source
Medline
License
Unknown

Abstract

Dendritic cells (DCs) produce major histocompatibility complex II (MHCII) in large amounts to function as professional antigen presenting cells. Paradoxically, DCs also ubiquitinate and degrade MHCII in a constitutive manner. Mice deficient in the MHCII-ubiquitinating enzyme membrane-anchored RING-CH1, or the ubiquitin-acceptor lysine of MHCII, exhibit a substantial reduction in the number of regulatory T (Treg) cells, but the underlying mechanism was unclear. Here we report that ubiquitin-dependent MHCII turnover is critical to maintain homeostasis of lipid rafts and the tetraspanin web in DCs. Lack of MHCII ubiquitination results in the accumulation of excessive quantities of MHCII in the plasma membrane, and the resulting disruption to lipid rafts and the tetraspanin web leads to significant impairment in the ability of DCs to engage and activate thymocytes for Treg cell differentiation. Thus, ubiquitin-dependent MHCII turnover represents a novel quality-control mechanism by which DCs maintain homeostasis of membrane domains that support DC's Treg cell-selecting function.

Report this publication

Statistics

Seen <100 times