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

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Clemente, Tiago ^{[1, 2]} ; Vieira, Narcisio J. ^{[1, 2]} ; Cerliani, Juan P. ^[3] ; Adrain, Colin ^[4] ; Luthi, Alexander ^[5] ; Dominguez, Mariana R. ^{[6, 7]} ; Yon, Monica ^{[1, 2]} ; Barrence, Fernanda C. ^[8] ; Riul, Thalita B. ^[9] ; Cummings, Richard D. ^[10] ; Zorn, Telma M. ^[8] ; Amigorena, Sebastian ^[11] ; Dias-Baruffi, Marcelo ^[9] ; Rodrigues, Mauricio M. ^{[6, 7]} ; Martin, Seamus J. ^[5] ; Rabinovich, Gabriel A. ^{[3, 12]} ; Amarante-Mendes, Gustavo P. ^{[1, 2, 5]}

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^[1] INCT, Inst Invest Imunol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Sao Paulo - Brazil

^[3] Consejo Nacl Invest Cient & Tecn CONICET, Inst Biol & Med Expt IBYME, Lab Inmunopatol, C1428, Buenos Aires, DF - Argentina

^[4] Inst Gulbenkian Ciencias, Oeiras - Portugal

^[5] Trinity Coll Dublin, Smurfit Inst, Dept Genet, Dublin - Ireland

^[6] Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, Sao Paulo, SP - Brazil

^[7] Univ Fed Sao Paulo, Escola Paulista Med, Ctr Terapia Celular Mol CTCMol, Sao Paulo, SP - Brazil

^[8] Univ Sao Paulo, Inst Ciencias Biomed, Dept Biol Celular & Desenvolvimento, Sao Paulo - Brazil

^[9] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, Ribeirao Preto - Brazil

^[10] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA - USA

^[11] PSL Res Univ, INSERM, U932, Inst Curie, Paris 05 - France

^[12] Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Quim Biol, C1428, Buenos Aires, DF - Argentina

• Tipo de documento: Artigo Científico
• Fonte: CELL DEATH & DISEASE; v. 8, DEC 2017.
• Citações Web of Science: 3

Resumo

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. (AU)

• Processo FAPESP: 14/16352-6 - Papel da galectina-1, rab2a, rab5a, rab17 e rab18 na citotoxicidade mediada por linfócitos T CD8
• Beneficiário: João Gustavo Pessini Amarante Mendes
• Modalidade de apoio: Auxílio à Pesquisa - Regular