Proteomic and functional analysis identifies galectin-1 as a novel regulatory component of the cytotoxic granule machinery
Secretory granules released by cytotoxic T lymphocytes (CTLs) are powerful weapons against intracellular microbes and tumor cells. Despite significant progress, there is still limited information on the molecular mechanisms implicated in target-driven degranulation, effector cell survival and compos...
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2017
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_20414889_v8_n12_pe3176_Clemente http://hdl.handle.net/20.500.12110/paper_20414889_v8_n12_pe3176_Clemente |
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paper:paper_20414889_v8_n12_pe3176_Clemente2023-06-08T16:33:11Z Proteomic and functional analysis identifies galectin-1 as a novel regulatory component of the cytotoxic granule machinery Fas ligand Fas protein, mouse Fasl protein, mouse galectin 1 tumor necrosis factor receptor superfamily member 6 animal C57BL mouse cell proliferation chemistry cytology cytotoxic T lymphocyte cytotoxicity degranulation gene expression profiling gene expression regulation genetics immunology knockout mouse lymphocyte activation male metabolism mouse proteomics secretory vesicle signal transduction Animals Cell Degranulation Cell Proliferation Cytotoxicity, Immunologic Fas Ligand Protein fas Receptor Galectin 1 Gene Expression Profiling Gene Expression Regulation Lymphocyte Activation Male Mice Mice, Inbred C57BL Mice, Knockout Proteomics Secretory Vesicles Signal Transduction T-Lymphocytes, Cytotoxic Secretory granules released by cytotoxic T lymphocytes (CTLs) are powerful weapons against intracellular microbes and tumor cells. Despite significant progress, there is still limited information on the molecular mechanisms implicated in target-driven degranulation, effector cell survival and composition and structure of the lytic granules. Here, using a proteomic approach we identified a panel of putative cytotoxic granule proteins, including some already known granule constituents and novel proteins that contribute to regulate the CTL lytic machinery. Particularly, we identified galectin-1 (Gal1), an endogenous immune regulatory lectin, as an integral component of the secretory granule machinery and unveil the unexpected function of this lectin in regulating CTL killing activity. Mechanistic studies revealed the ability of Gal1 to control the non-secretory lytic pathway by influencing Fas-Fas ligand interactions. This study offers new insights on the composition of the cytotoxic granule machinery, highlighting the dynamic cross talk between secretory and non-secretory pathways in controlling CTL lytic function. 2017 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_20414889_v8_n12_pe3176_Clemente http://hdl.handle.net/20.500.12110/paper_20414889_v8_n12_pe3176_Clemente |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Fas ligand Fas protein, mouse Fasl protein, mouse galectin 1 tumor necrosis factor receptor superfamily member 6 animal C57BL mouse cell proliferation chemistry cytology cytotoxic T lymphocyte cytotoxicity degranulation gene expression profiling gene expression regulation genetics immunology knockout mouse lymphocyte activation male metabolism mouse proteomics secretory vesicle signal transduction Animals Cell Degranulation Cell Proliferation Cytotoxicity, Immunologic Fas Ligand Protein fas Receptor Galectin 1 Gene Expression Profiling Gene Expression Regulation Lymphocyte Activation Male Mice Mice, Inbred C57BL Mice, Knockout Proteomics Secretory Vesicles Signal Transduction T-Lymphocytes, Cytotoxic |
| spellingShingle |
Fas ligand Fas protein, mouse Fasl protein, mouse galectin 1 tumor necrosis factor receptor superfamily member 6 animal C57BL mouse cell proliferation chemistry cytology cytotoxic T lymphocyte cytotoxicity degranulation gene expression profiling gene expression regulation genetics immunology knockout mouse lymphocyte activation male metabolism mouse proteomics secretory vesicle signal transduction Animals Cell Degranulation Cell Proliferation Cytotoxicity, Immunologic Fas Ligand Protein fas Receptor Galectin 1 Gene Expression Profiling Gene Expression Regulation Lymphocyte Activation Male Mice Mice, Inbred C57BL Mice, Knockout Proteomics Secretory Vesicles Signal Transduction T-Lymphocytes, Cytotoxic Proteomic and functional analysis identifies galectin-1 as a novel regulatory component of the cytotoxic granule machinery |
| topic_facet |
Fas ligand Fas protein, mouse Fasl protein, mouse galectin 1 tumor necrosis factor receptor superfamily member 6 animal C57BL mouse cell proliferation chemistry cytology cytotoxic T lymphocyte cytotoxicity degranulation gene expression profiling gene expression regulation genetics immunology knockout mouse lymphocyte activation male metabolism mouse proteomics secretory vesicle signal transduction Animals Cell Degranulation Cell Proliferation Cytotoxicity, Immunologic Fas Ligand Protein fas Receptor Galectin 1 Gene Expression Profiling Gene Expression Regulation Lymphocyte Activation Male Mice Mice, Inbred C57BL Mice, Knockout Proteomics Secretory Vesicles Signal Transduction T-Lymphocytes, Cytotoxic |
| description |
Secretory granules released by cytotoxic T lymphocytes (CTLs) are powerful weapons against intracellular microbes and tumor cells. Despite significant progress, there is still limited information on the molecular mechanisms implicated in target-driven degranulation, effector cell survival and composition and structure of the lytic granules. Here, using a proteomic approach we identified a panel of putative cytotoxic granule proteins, including some already known granule constituents and novel proteins that contribute to regulate the CTL lytic machinery. Particularly, we identified galectin-1 (Gal1), an endogenous immune regulatory lectin, as an integral component of the secretory granule machinery and unveil the unexpected function of this lectin in regulating CTL killing activity. Mechanistic studies revealed the ability of Gal1 to control the non-secretory lytic pathway by influencing Fas-Fas ligand interactions. This study offers new insights on the composition of the cytotoxic granule machinery, highlighting the dynamic cross talk between secretory and non-secretory pathways in controlling CTL lytic function. |
| title |
Proteomic and functional analysis identifies galectin-1 as a novel regulatory component of the cytotoxic granule machinery |
| title_short |
Proteomic and functional analysis identifies galectin-1 as a novel regulatory component of the cytotoxic granule machinery |
| title_full |
Proteomic and functional analysis identifies galectin-1 as a novel regulatory component of the cytotoxic granule machinery |
| title_fullStr |
Proteomic and functional analysis identifies galectin-1 as a novel regulatory component of the cytotoxic granule machinery |
| title_full_unstemmed |
Proteomic and functional analysis identifies galectin-1 as a novel regulatory component of the cytotoxic granule machinery |
| title_sort |
proteomic and functional analysis identifies galectin-1 as a novel regulatory component of the cytotoxic granule machinery |
| publishDate |
2017 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_20414889_v8_n12_pe3176_Clemente http://hdl.handle.net/20.500.12110/paper_20414889_v8_n12_pe3176_Clemente |
| _version_ |
1768544753122541568 |