MARCH9-mediated ubiquitination regulates MHC i export from the TGN
© 2017 Australasian Society for Immunology Inc. All rights reserved. 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....
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
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Nature Publishing Group
2017
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| Online Access: | http://hdl.handle.net/20.500.11937/69150 |
| _version_ | 1848761980667559936 |
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| author | De Angelis Rigotti, F. De Gassart, A. Pforr, Christof Cano, F. N'Guessan, P. Combes, A. Camossetto, V. Lehner, P. Pierre, P. Gatti, E. |
| author_facet | De Angelis Rigotti, F. De Gassart, A. Pforr, Christof Cano, F. N'Guessan, P. Combes, A. Camossetto, V. Lehner, P. Pierre, P. Gatti, E. |
| author_sort | De Angelis Rigotti, F. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2017 Australasian Society for Immunology Inc. All rights reserved. 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. |
| first_indexed | 2025-11-14T10:40:18Z |
| format | Journal Article |
| id | curtin-20.500.11937-69150 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:40:18Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-691502018-06-29T12:35:37Z MARCH9-mediated ubiquitination regulates MHC i export from the TGN De Angelis Rigotti, F. De Gassart, A. Pforr, Christof Cano, F. N'Guessan, P. Combes, A. Camossetto, V. Lehner, P. Pierre, P. Gatti, E. © 2017 Australasian Society for Immunology Inc. All rights reserved. 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. 2017 Journal Article http://hdl.handle.net/20.500.11937/69150 10.1038/icb.2017.44 Nature Publishing Group restricted |
| spellingShingle | De Angelis Rigotti, F. De Gassart, A. Pforr, Christof Cano, F. N'Guessan, P. Combes, A. Camossetto, V. Lehner, P. Pierre, P. Gatti, E. MARCH9-mediated ubiquitination regulates MHC i export from the TGN |
| title | MARCH9-mediated ubiquitination regulates MHC i export from the TGN |
| title_full | MARCH9-mediated ubiquitination regulates MHC i export from the TGN |
| title_fullStr | MARCH9-mediated ubiquitination regulates MHC i export from the TGN |
| title_full_unstemmed | MARCH9-mediated ubiquitination regulates MHC i export from the TGN |
| title_short | MARCH9-mediated ubiquitination regulates MHC i export from the TGN |
| title_sort | march9-mediated ubiquitination regulates mhc i export from the tgn |
| url | http://hdl.handle.net/20.500.11937/69150 |