Role of adaptor protein SLAT in FcgammaR mediated phagocytosis in macrophages.

摘要

SLAT (SWAP 70-like adapter protein of T cells) is an adapter protein expressed in cells of the hematopoietic system. SLAT has been shown to interact with and affect the function of the small GTPase Rac1 in fibroblasts. In these nonhematopoietic cell models, over-expression of SLAT and the subsequent SLATRac interaction appears to cause changes in F-actin and cytoskeletal reorganization. In T cells, SLAT expression appears to regulate the development of T helper cells and SLAT knockout animals develop a lupus-like syndrome, although a molecular mechanism for either of these functions in unclear.;We find that SLAT is expressed in murine macrophages. Over-expression of SLAT inhibits the IgG Fcγ receptor-mediated phagocytic ability of the macrophage cell line THP1. In primary, bone marrow-derived macrophages, SLAT protein was recruited to the early phagosomes formed upon Fcγ receptor engagement. SLAT recruitment to the phagosome required that the macrophages express at least one isoform of Rac (Rac1 or Rac2), since SLAT recruitment was absent in macrophages of Rac-deficient mice. Macrophages derived from animals lacking SLAT showed an elevation in the rate of Fcγ receptor-mediated phagocytosis. The absence of SLAT was associated with an increase in the amount of F-actin formed around these phagosomes as well as an increase in the amount of Rac1 protein recruited to the phagosome. Our results suggest a model in which SLAT acts as a gate-keeper for the amount of Rac1 recruited to the phagosomes. By controlling the amount of Rac1, SLAT is able to regulate F-actin accumulation and consequently govern the rate of phagocytosis.