摘要：

Apoptotic cells generated by programmed cell death are rapidly removed to prevent inflammatory and autoimmune responses and maintain tissue homeostasis.During this process,apoptotic cells expose"eat me"signals,which are recognized by phagocytes to trigger signaling cascades,leading to internalization and degradation of cell corpses.Phosphatidylserine(PS),which is normally restricted to the inner leaflet of plasma membranes,is exposed on the surface of apoptotic cells,thus distinguishing the dying cells from normal living cells and serving as a general"eat me"signal for engulfment.Using genetic approaches,we have identified two PS-binding proteins,TTR-52 and NRF-5,which are required for efficient clearance of apoptotic cells.Our findings indicate that TTR-52 acts as a bridging molecule to mediate cell corpse recognition by cross-linking the PS"eat me"signal on apoptotic cells with the CED-1receptor on phagocytes~1.NRF-5,a secreted LPS-binding/lipid transfer family protein,acts with TTR-52 and CED-7 to mediate PS transfer from apoptotic cells to engulfing cells and thus promotes recognition and engulfment by phagocytes2.Recently,we identified two additional TTR-52 family proteins that cluster specifically around cell corpses upon secretion.Interestingly,recognition of apoptotic cells by these two TTR-52 family proteins is affected by the mutation in ced-7 but not tat-1,a feature similar to NRF-5 but distinct from TTR-52.Our study suggests that multiple secreted PS-binding proteins act coordinately to mediate recognition of apoptotic cells.Phospholipids are building blocks of lipid bilayers and key regulators of membrane trafficking events.By using genetically coded reporters,we investigated the dynamics of various phospholipids during cell corpse clearance and analyzed their roles in phagosome formation and maturation.We found that internalization of cell corpses is regulated by coordinated actions of a couple of phosphoinositides.In the meeting,I will present our recent work regarding phospholipid signaling involved in apoptotic cell recognition and internalization.

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