PMID- 29371232 OWN - NLM STAT- MEDLINE DCOM- 20190318 LR - 20190709 IS - 1540-8140 (Electronic) IS - 0021-9525 (Print) IS - 0021-9525 (Linking) VI - 217 IP - 4 DP - 2018 Apr 2 TI - MARCH1 protects the lipid raft and tetraspanin web from MHCII proteotoxicity in dendritic cells. PG - 1395-1410 LID - 10.1083/jcb.201611141 [doi] AB - 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. CI - (c) 2018 Oh et al. FAU - Oh, Jaehak AU - Oh J AUID- ORCID: 0000-0003-3079-5927 AD - Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA. AD - Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA. FAU - Perry, Justin S A AU - Perry JSA AD - Department of Pathology, University of California, San Francisco, San Francisco, CA. FAU - Pua, Heather AU - Pua H AUID- ORCID: 0000-0002-9271-2608 AD - Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA. AD - Department of Pathology, University of California, San Francisco, San Francisco, CA. FAU - Irgens-Moller, Nicole AU - Irgens-Moller N AD - Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA. AD - Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA. FAU - Ishido, Satoshi AU - Ishido S AD - Department of Microbiology, Hyogo College of Medicine 1-1, Mukogawa-cho, Nishinomiya, Japan. FAU - Hsieh, Chyi-Song AU - Hsieh CS AD - Department of Internal Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, MO. FAU - Shin, Jeoung-Sook AU - Shin JS AUID- ORCID: 0000-0002-0711-8234 AD - Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA jeoung-sook.shin@ucsf.edu. AD - Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA. LA - eng GR - R01 AI079187/AI/NIAID NIH HHS/United States GR - R01 GM105800/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20180125 PL - United States TA - J Cell Biol JT - The Journal of cell biology JID - 0375356 RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Receptors, Antigen, T-Cell) RN - 0 (Tetraspanins) RN - EC 2.3.2.27 (MARCH1 protein, mouse) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM MH - Adoptive Transfer MH - Animals MH - *Cell Communication MH - Cell Differentiation MH - Cells, Cultured MH - Coculture Techniques MH - Dendritic Cells/*enzymology/immunology/pathology MH - Histocompatibility Antigens Class II/genetics/immunology/*metabolism MH - Homeostasis MH - Lymphocyte Activation MH - Membrane Microdomains/*enzymology/immunology/pathology MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Phenotype MH - Receptors, Antigen, T-Cell/genetics/immunology/metabolism MH - Signal Transduction MH - T-Lymphocytes, Regulatory/immunology/*metabolism/transplantation MH - Tetraspanins/immunology/*metabolism MH - Thymocytes/immunology/*metabolism MH - Ubiquitin-Protein Ligases/genetics/immunology/*metabolism MH - Ubiquitination PMC - PMC5881489 EDAT- 2018/01/27 06:00 MHDA- 2019/03/19 06:00 PMCR- 2018/10/02 CRDT- 2018/01/27 06:00 PHST- 2016/11/22 00:00 [received] PHST- 2017/10/25 00:00 [revised] PHST- 2018/01/08 00:00 [accepted] PHST- 2018/01/27 06:00 [pubmed] PHST- 2019/03/19 06:00 [medline] PHST- 2018/01/27 06:00 [entrez] PHST- 2018/10/02 00:00 [pmc-release] AID - jcb.201611141 [pii] AID - 201611141 [pii] AID - 10.1083/jcb.201611141 [doi] PST - ppublish SO - J Cell Biol. 2018 Apr 2;217(4):1395-1410. doi: 10.1083/jcb.201611141. Epub 2018 Jan 25.