Fig. 1

TAM - PtdSer association and the uptake of apoptotic cells. Apoptotic cells (ACs) externalize phosphatidylserine (PtdSer) which is bound by the TAM ligands GAS6 and PROS1. This binding occurs at the GLA domain, present at the amino terminus of the ligands, and is enhanced by the presence of calcium ions, depicted by green ovals. The carboxyl terminal of PROS1 and GAS6 binds to the extracellular domains of the TAM receptors, present on professional phagocytes such as retinal pigment epithelium, Sertoli cells, osteoclasts, macrophages and DCs. TAM receptor activation is optimal in the presence of both ligands and PtdSer. By binding PtdSer on one side and to TAM receptors on the phagocytic cell, PROS1 and GAS6 function as bridging molecules physically linking the phagocyte to the engulfed PtdSer-decorated moiety. In case of macrophage and dendritic cell phagocytes, AC uptake and TAM activation also results in shutting inflammatory signaling and cytokine secretion. Abbreviations: Ca – Calcium ion; PtdSer – phosphatidylserine; TAM – TYRO3, AXL, MERTK, PROS1 – protein S; GAS6 – growth arrest specific 6