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

TIAGO CLEMENTE; NARCISIO J VIEIRA ; JUAN P CERLIANI; COLIN ADRAIN; ALEXANDER LUTHI; MARIANA R DOMINGUEZ; MONICA YON; FERNANDA C BARRENCE; THALITA B RIUL; RICHARD D CUMMINGS; TELMA M ZORN; SEBASTIAN AMIGORENA; MARCELO DIAS-BARUFFI; MAURÍCIO M RODRIGUES; SEAMUS J MARTIN; GABRIEL A RABINOVICH; GUSTAVO P AMARANTE-MENDES

CELL DEATH AND DISEASE

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 2017

Secretory granules released by cytotoxic T lymphocytes (CTLs) are powerful weapons against intracellular microbes and tumorcells. Despite significant progress, there is still limited information on the molecular mechanisms implicated in target-drivendegranulation, effector cell survival and composition and structure of the lytic granules. Here, using a proteomic approach weidentified a panel of putative cytotoxic granule proteins, including some already known granule constituents and novel proteinsthat contribute to regulate the CTL lytic machinery. Particularly, we identified galectin-1 (Gal1), an endogenous immune regulatorylectin, as an integral component of the secretory granule machinery and unveil the unexpected function of this lectin in regulatingCTL 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 thedynamic cross talk between secretory and non-secretory pathways in controlling CTL lytic function.Cell Death and Disease (2017) 8, e; doi:10.1038/cddis.2017.506; published online xx xxx 2017