Regulation of phagocytosis by TAM receptors and their ligands

Abstract

The TAM family of receptors is preferentially expressed by professional and non-professional phagocytes, including macrophages, dendritic cells and natural killer cells in the immune system, osteoclasts in bone, Sertoli cells in testis, and retinal pigmental epithelium cells in the retina. Mutations in the Mertk single gene or in different combinations of the double or triple gene mutations in the same cell cause complete or partial impairment in phagocytosis of their preys; and as a result, either the normal apoptotic cells cannot be efficiently removed or the tissue neighbor cells die by apoptosis. This scenario of TAM regulation represents a widely adapted model system used by phagocytes in all different tissues. The present review will summarize current known functional roles of TAM receptors and their ligands, Gas 6 and protein S, in the regulation of phagocytosis.

Fig. 1

Domain structure of Tyro 3, Axl and Mertk family receptors (A) and ligands, Gas 6 and protein S (B). The tyrosine (Y) residues and the flanking sequences listed in (A) represent the mouse Tyro 3; and those important for phagocytosis regulation on Axl and Mertk are listed in (C). See text for details.

Fig. 2

Cell number per 200-μm of segment at 200 μm temporally to optic nerve in a horizontal section of the retina in WT, Mertk^−/− and TAM triple mutant mice. Counts were performed from the outer nuclear layer (ONL; i.e., photoreceptor layer), inner nuclear layer (INL), and ganglion cell layer (GCL).