3 research outputs found
Adaptor Protein SLAT Modulates Fcγ Receptor-mediated Phagocytosis in Murine Macrophages*
SLAT (SWAP-70-like adaptor protein of T cells) is an adaptor protein
expressed in cells of the hematopoietic system. SLAT interacts with and alters
the function of small GTPase Rac1 in fibroblasts. In these nonhematopoietic
models, the SLAT-Rac interaction leads to changes in F-actin and causes
cytoskeletal reorganization. In T cells, SLAT expression regulates the
development of T helper cells through Cdc42- and Rac1-mediated activation of
the NF-AT transcription factor. Here we show that SLAT is expressed in
macrophages. Overexpression of SLAT in a macrophage cell line inhibits the IgG
Fcγ receptor-mediated phagocytic ability of THP1 cells. In bone
marrow-derived macrophages, SLAT protein is recruited to the early phagosomes
formed via Fcγ receptor engagement. SLAT recruitment to the phagosome
was most efficient when the macrophages express at least one isoform of Rac
(Rac1 or Rac2), because SLAT recruitment was reduced in macrophages of
Rac-deficient mice. Macrophages derived from animals lacking SLAT show an
elevation in the rate of Fcγ receptor-mediated phagocytosis. The absence
of SLAT is 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 that SLAT acts as a gatekeeper
for the amount of Rac recruited to the phagosomes formed by Fcγ receptor
engagement and thus is able to regulate F-actin re-organization and
consequently phagocytosis