SLAMF1 is required for TLR4-mediated TRAM-TRIF-dependent signaling in human macrophages.
J Cell Biol
; 217(4): 1411-1429, 2018 04 02.
Article
em En
| MEDLINE
| ID: mdl-29440514
ABSTRACT
Signaling lymphocytic activation molecule family 1 (SLAMF1) is an Ig-like receptor and a costimulatory molecule that initiates signal transduction networks in a variety of immune cells. In this study, we report that SLAMF1 is required for Toll-like receptor 4 (TLR4)-mediated induction of interferon ß (IFNß) and for killing of Gram-negative bacteria by human macrophages. We found that SLAMF1 controls trafficking of the Toll receptor-associated molecule (TRAM) from the endocytic recycling compartment (ERC) to Escherichia coli phagosomes. In resting macrophages, SLAMF1 is localized to ERC, but upon addition of E. coli, it is trafficked together with TRAM from ERC to E. coli phagosomes in a Rab11-dependent manner. We found that endogenous SLAMF1 protein interacted with TRAM and defined key interaction domains as amino acids 68 to 95 of TRAM as well as 15 C-terminal amino acids of SLAMF1. Interestingly, the SLAMF1-TRAM interaction was observed for human but not mouse proteins. Overall, our observations suggest that SLAMF1 is a new target for modulation of TLR4-TRAM-TRIF inflammatory signaling in human cells.
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Base de dados:
MEDLINE
Assunto principal:
Endossomos
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Proteínas Adaptadoras de Transporte Vesicular
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Proteínas Adaptadoras de Transdução de Sinal
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Receptor 4 Toll-Like
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Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária
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Ativação de Macrófagos
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Macrófagos
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article