One of the key features of the plasma membrane is the asymmetrical distribution of phospholipids across it. Especially, phosphatidylserine (PS) exclusively locates on its inner leaflet. Thus, the exposure of PS on the surface of cells could function as a signal initiating various cellular processes such as phagocytosis of apoptotic cells called efferocytosis, blood clotting, muscle formation, and viral entry. Indeed, PS on apoptotic cells stimulates phagocytes to engulf them and functions as an essential ligand for efferocytosis. Due to the importance of PS in efferocytosis, the existence of the PS receptor had been conceived. However, the PS receptor had not been revealed for a long time. Thus, the first identification of the PS receptor was significant excitement. Tim-4, a member of the T cell immunoglobulin and mucin domain containing family of genes, was one of PS receptors which first identified and received the greatest attention due to its expression in macrophages and relevance to autoimmune and allergic diseases. This review will serve to provide a comprehensive overview of Tim proteins as PS receptors.
Keywords: Efferocytosis; Phosphatidylserine; Phosphatidylserine receptor; Tim-4; Timd.