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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Autores principales:	Clemente, T., Vieira, N.J., Cerliani, J.P., Adrain, C., Luthi, A., Dominguez, M.R., Yon, M., Barrence, F.C., Riul, T.B., Cummings, R.D., Zorn, T.M., Amigorena, S., Dias-Baruffi, M., Rodrigues, M.M., Martin, S.J., Rabinovich, G.A., Amarante-Mendes, G.P.
Formato:	JOUR
Materias:	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
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_20414889_v8_n12_pe3176_Clemente
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_20414889_v8_n12_pe3176_Clemente
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spelling	todo:paper_20414889_v8_n12_pe3176_Clemente2023-10-03T16:37:56Z Proteomic and functional analysis identifies galectin-1 as a novel regulatory component of the cytotoxic granule machinery Clemente, T. Vieira, N.J. Cerliani, J.P. Adrain, C. Luthi, A. Dominguez, M.R. Yon, M. Barrence, F.C. Riul, T.B. Cummings, R.D. Zorn, T.M. Amigorena, S. Dias-Baruffi, M. Rodrigues, M.M. Martin, S.J. Rabinovich, G.A. Amarante-Mendes, G.P. 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar 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 Clemente, T. Vieira, N.J. Cerliani, J.P. Adrain, C. Luthi, A. Dominguez, M.R. Yon, M. Barrence, F.C. Riul, T.B. Cummings, R.D. Zorn, T.M. Amigorena, S. Dias-Baruffi, M. Rodrigues, M.M. Martin, S.J. Rabinovich, G.A. Amarante-Mendes, G.P. 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.
format	JOUR
author	Clemente, T. Vieira, N.J. Cerliani, J.P. Adrain, C. Luthi, A. Dominguez, M.R. Yon, M. Barrence, F.C. Riul, T.B. Cummings, R.D. Zorn, T.M. Amigorena, S. Dias-Baruffi, M. Rodrigues, M.M. Martin, S.J. Rabinovich, G.A. Amarante-Mendes, G.P.
author_facet	Clemente, T. Vieira, N.J. Cerliani, J.P. Adrain, C. Luthi, A. Dominguez, M.R. Yon, M. Barrence, F.C. Riul, T.B. Cummings, R.D. Zorn, T.M. Amigorena, S. Dias-Baruffi, M. Rodrigues, M.M. Martin, S.J. Rabinovich, G.A. Amarante-Mendes, G.P.
author_sort	Clemente, T.
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
url	http://hdl.handle.net/20.500.12110/paper_20414889_v8_n12_pe3176_Clemente
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Proteomic and functional analysis identifies galectin-1 as a novel regulatory component of the cytotoxic granule machinery

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