Proteomic and functional analysis identifies galectin-1 as a novel regulatory component of the cytotoxic granule machinery

Proteomic and functional analysis identifies galectin-1 as a novel regulatory component of the cytotoxic granule machinery

Author Clemente, Tiago Google Scholar
Vieira, Narcisio J. Google Scholar
Cerliani, Juan P. Google Scholar
Adrain, Colin Google Scholar
Luthi, Alexander Google Scholar
Dominguez, Mariana R. Autor UNIFESP Google Scholar
Yon, Monica Google Scholar
Barrence, Fernanda C. Google Scholar
Riul, Thalita B. Google Scholar
Cummings, Richard D. Google Scholar
Zorn, Telma M. Google Scholar
Amigorena, Sebastian Google Scholar
Dias-Baruffi, Marcelo Google Scholar
Autor UNIFESP Google Scholar
Martin, Seamus J. Google Scholar
Rabinovich, Gabriel A. Google Scholar
Amarante-Mendes, Gustavo P. Google Scholar
Abstract 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.
xmlui.dri2xhtml.METS-1.0.item-coverage London
Language English
Sponsor Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Brazil)
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [CNPq-31194-/2015-8]
Science Foundation Ireland
Agencia de Promocion Cientifica y Tecnologica (PICT)
FAPESP [2014/16352-6]
Grant number CNPq-31194-/2015-8]
FAPESP [2014/16352-6]
Date 2017
Published in Cell Death & Disease. London, v. 8, p. -, 2017.
ISSN 2041-4889 (Sherpa/Romeo, impact factor)
Publisher Nature Publishing Group
Extent -
Origin http://dx.doi.org/10.1038/cddis.2017.506
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000425166800002
URI https://repositorio.unifesp.br/handle/11600/54018

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