Physiological substrates and ontogeny-specific expression of the ubiquitin ligases MARCH1 and MARCH8
MARCH1 and MARCH8 are ubiquitin ligases that control the expression and trafficking of critical immunoreceptors. Understanding of their function is hampered by three major knowledge gaps: (i) it is unclear which cell types utilize these ligases; (ii) their level of redundancy is unknown; and (iii) m...
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Elsevier
2021
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oai:doaj.org-article:6a717133d4e94e62b63aa75cdf8d87bd2021-12-04T04:35:49ZPhysiological substrates and ontogeny-specific expression of the ubiquitin ligases MARCH1 and MARCH82590-255510.1016/j.crimmu.2021.10.004https://doaj.org/article/6a717133d4e94e62b63aa75cdf8d87bd2021-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2590255521000214https://doaj.org/toc/2590-2555MARCH1 and MARCH8 are ubiquitin ligases that control the expression and trafficking of critical immunoreceptors. Understanding of their function is hampered by three major knowledge gaps: (i) it is unclear which cell types utilize these ligases; (ii) their level of redundancy is unknown; and (iii) most of their putative substrates have been described in cell lines, often overexpressing MARCH1 or MARCH8, and it is unclear which substrates are regulated by either ligase in vivo. Here we address these questions by systematically analyzing the immune cell repertoire of MARCH1- or MARCH8-deficient mice, and applying unbiased proteomic profiling of the plasma membrane of primary cells to identify MARCH1 and MARCH8 substrates. Only CD86 and MHC II were unequivocally identified as immunoreceptors regulated by MARCH1 and MARCH8, but each ligase carried out its function in different tissues. MARCH1 regulated MHC II and CD86 in professional and “atypical” antigen presenting cells of hematopoietic origin, including neutrophils, eosinophils and monocytes. MARCH8 only operated in non-hematopoietic cells, such as thymic and alveolar epithelial cells. Our results establish the tissue-specific functions of MARCH1 and MARCH8 in regulation of immune receptor expression and reveal that the range of cells constitutively endowed with antigen-presentation capacity is wider than generally appreciated.Patrick SchriekHaiyin LiuAlan C. ChingPauline HuangNishma GuptaKayla R. WilsonMinHsuang TsaiYuting YanChristophe F. MacriLaura F. DagleyGiuseppe InfusiniAndrew I. WebbHamish E.G. McWilliamSatoshi IshidoJustine D. MinternJose A. VilladangosElsevierarticleAntigen presentation and processingRegulation of surface stimulatory moleculesMARCH E3 ubiquitin ligasesPrimary cell analysisSpecialties of internal medicineRC581-951ENCurrent Research in Immunology, Vol 2, Iss , Pp 218-228 (2021) |
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DOAJ |
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EN |
| topic |
Antigen presentation and processing Regulation of surface stimulatory molecules MARCH E3 ubiquitin ligases Primary cell analysis Specialties of internal medicine RC581-951 |
| spellingShingle |
Antigen presentation and processing Regulation of surface stimulatory molecules MARCH E3 ubiquitin ligases Primary cell analysis Specialties of internal medicine RC581-951 Patrick Schriek Haiyin Liu Alan C. Ching Pauline Huang Nishma Gupta Kayla R. Wilson MinHsuang Tsai Yuting Yan Christophe F. Macri Laura F. Dagley Giuseppe Infusini Andrew I. Webb Hamish E.G. McWilliam Satoshi Ishido Justine D. Mintern Jose A. Villadangos Physiological substrates and ontogeny-specific expression of the ubiquitin ligases MARCH1 and MARCH8 |
| description |
MARCH1 and MARCH8 are ubiquitin ligases that control the expression and trafficking of critical immunoreceptors. Understanding of their function is hampered by three major knowledge gaps: (i) it is unclear which cell types utilize these ligases; (ii) their level of redundancy is unknown; and (iii) most of their putative substrates have been described in cell lines, often overexpressing MARCH1 or MARCH8, and it is unclear which substrates are regulated by either ligase in vivo. Here we address these questions by systematically analyzing the immune cell repertoire of MARCH1- or MARCH8-deficient mice, and applying unbiased proteomic profiling of the plasma membrane of primary cells to identify MARCH1 and MARCH8 substrates. Only CD86 and MHC II were unequivocally identified as immunoreceptors regulated by MARCH1 and MARCH8, but each ligase carried out its function in different tissues. MARCH1 regulated MHC II and CD86 in professional and “atypical” antigen presenting cells of hematopoietic origin, including neutrophils, eosinophils and monocytes. MARCH8 only operated in non-hematopoietic cells, such as thymic and alveolar epithelial cells. Our results establish the tissue-specific functions of MARCH1 and MARCH8 in regulation of immune receptor expression and reveal that the range of cells constitutively endowed with antigen-presentation capacity is wider than generally appreciated. |
| format |
article |
| author |
Patrick Schriek Haiyin Liu Alan C. Ching Pauline Huang Nishma Gupta Kayla R. Wilson MinHsuang Tsai Yuting Yan Christophe F. Macri Laura F. Dagley Giuseppe Infusini Andrew I. Webb Hamish E.G. McWilliam Satoshi Ishido Justine D. Mintern Jose A. Villadangos |
| author_facet |
Patrick Schriek Haiyin Liu Alan C. Ching Pauline Huang Nishma Gupta Kayla R. Wilson MinHsuang Tsai Yuting Yan Christophe F. Macri Laura F. Dagley Giuseppe Infusini Andrew I. Webb Hamish E.G. McWilliam Satoshi Ishido Justine D. Mintern Jose A. Villadangos |
| author_sort |
Patrick Schriek |
| title |
Physiological substrates and ontogeny-specific expression of the ubiquitin ligases MARCH1 and MARCH8 |
| title_short |
Physiological substrates and ontogeny-specific expression of the ubiquitin ligases MARCH1 and MARCH8 |
| title_full |
Physiological substrates and ontogeny-specific expression of the ubiquitin ligases MARCH1 and MARCH8 |
| title_fullStr |
Physiological substrates and ontogeny-specific expression of the ubiquitin ligases MARCH1 and MARCH8 |
| title_full_unstemmed |
Physiological substrates and ontogeny-specific expression of the ubiquitin ligases MARCH1 and MARCH8 |
| title_sort |
physiological substrates and ontogeny-specific expression of the ubiquitin ligases march1 and march8 |
| publisher |
Elsevier |
| publishDate |
2021 |
| url |
https://doaj.org/article/6a717133d4e94e62b63aa75cdf8d87bd |
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