Beginnings of a Good Apoptotic Meal: The Find-Me and Eat-Me Signaling Pathways

Department of Microbiology, Immunology, and Cancer Biology, Center for Cell Clearance, University of Virginia, Charlottesville, VA 22908, USA.
Immunity (Impact Factor: 21.56). 10/2011; 35(4):445-55. DOI: 10.1016/j.immuni.2011.09.004
Source: PubMed


Prompt and efficient clearance of apoptotic cells is necessary to prevent secondary necrosis of dying cells and to avoid immune responses to autoantigens. Recent studies have shed light on how apoptotic cells through soluble "find-me" signals advertise their presence to phagocytes at the earliest stages of cell death. Phagocytes sense the find-me signal gradient, and in turn the presence of dying cells, and migrate to their vicinity. The apoptotic cells also expose specific "eat-me" signals on their surface that are recognized by phagocytes through specific engulfment receptors. This review covers the recent progress in the areas of find-me and eat-me signals and how these relate to prompt and immunologically silent clearance of apoptotic cells.

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Available from: Kodi Ravichandran, May 26, 2014
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    • "A summary of characteristics of these PVEERs is shown in Table 1. The key property that these proteins or complexes utilize to enhance virus entry is their ability to bind PtdSer and a native function of all of these receptors is to bind and clear apoptotic bodies (Ravichandran, 2011). Mutation of residues involved in PtdSer binding or complex formation results in inhibition of PVEER function (Morizono et al., 2011; Meertens et al., 2012; Moller-Tank et al., 2013; Morizono and Chen, 2014). "
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    ABSTRACT: A variety of both RNA and DNA viruses envelop their capsids in a lipid bilayer. One of the more recently appreciated benefits this envelope is incorporation of phosphatidylserine (PtdSer). Surface exposure of PtdSer disguises viruses as apoptotic bodies; tricking cells into engulfing virions. This mechanism is termed apoptotic mimicry. Several PtdSer receptors have been identified to enhance virus entry and we have termed this group of proteins PtdSer-mediated virus entry enhancing receptors or PVEERs. These receptors enhance entry of a range of enveloped viruses. Internalization of virions by PVEERs provides a broad mechanism of entry with little investment by the virus itself. PVEERs may allow some viruses to attach to cells, thereby making viral glycoprotein/cellular receptor interactions more probable. Alternatively, other viruses may rely entirely on PVEERs for internalization into endosomes. This review provides an overview of PtdSer receptors that serve as PVEERs and the biology behind virion/PVEER interaction.
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    • "The ingestion of apoptotic cells (termed " efferocytosis " ) by phagocytes has been shown to trigger release of molecules such as transforming growth factor ␤ (TGF␤ ), interleukin-10 (IL-10), and prostaglandin E2 (PGE2), which are thought to be mediators of immunosuppression and immunological tolerance to self-antigens (Ravichandran, 2011; Savill et al., 2002; Michlewska et al., 2007). Apoptotic cells are recognized by the receptors on the phagocytes through the so-called 'eat-me' signals on the surface of the apoptotic cell (Ravichandran, 2011). The molecules downstream of these receptors are partly identified , including small GTPase Rac-1, Cdc42, and RhoG which belong to Rho family of GTPase. "
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    • "Often, the vacuole fuses with the endolysosomal network, which includes early endosomes, late endosomes and lysosomes. Engulfment can be distinguished from other kinds of endocytic activity such as clathrin-mediated endocytosis, caveolin-mediated endocytosis and others, not only by the larger size of vesicles created by engulfment, but also by the significant involvement of the actin cytoskeleton (Kerr and Teasdale, 2009; Ravichandran, 2011; Flannagan et al., 2012). Phosphoinositides (PIs) are phospholipids which localize predominantly to the cytosolic face of cellular membranes. "
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