Fig. 3.

Signaling pathways elicited by three PtdSer recognition receptors. Binding of the apoptotic cell to the phagocyte triggers signaling pathways. BAI1 is a 7-transmembrane receptor that directly binds the PtdSer on the surface of an apoptotic cell, resulting in the recruitment of the Engulfment and cell motility (ELMO)/Downstream of Crk (DOCK) complex, which functions as a guanine exchange factor for the small GTPase Rac³⁹. Rac activation promotes actin cytoskeleton remodeling required for the engulfment of the apoptotic corpse. Integrins α_Vβ₃ or α_Vβ₅ and the Tyro Axl Mer (TAM) family receptors bind apoptotic cells indirectly, via PtdSer-bound bridging molecules MFG-E8, Gas6 or ProteinS, resulting in the activation of the focal adhesion kinase (FAK) and contributing to the activation of Rac¹¹⁴. TAM receptors are tyrosine kinases that also activate cell signaling pathways involving the kinases Src and phosphatidylinositol-3-kinase (PI3K) and phospholipase C (PLC)^{114, 115}. TIM4 functions as a tethering receptor bringing the apoptotic cell in contact with signaling engulfment receptors, and signal through co-receptors. The extent of the connection between the signals elicited by different engulfment receptors awaits further characterization.