Caenorhabditis elegans transthyretin-like protein TTR-52 mediates recognition of apoptotic cells by the CED-1 phagocyte receptor

Abstract

During apoptosis, dying cells are swiftly removed by phagocytes. How apoptotic cells are recognized by phagocytes is not fully understood. Here we report the identification and characterization of the C. elegans ttr-52 gene, which is required for efficient cell corpse engulfment and encodes a transthyretin-like protein. The TTR-52 protein is expressed in and secreted from C. elegans endoderm and clusters around apoptotic cells. Genetic analysis indicates that TTR-52 acts in the cell corpse engulfment pathway mediated by CED-1, CED-6, and CED-7 and affects clustering of the phagocyte receptor CED-1 around apoptotic cells. Interestingly, TTR-52 recognizes surface exposed phosphatidylserine (PS) in vivo and binds to both PS and the extracellular domain of CED-1 in vitro. Therefore, TTR-52 is the first bridging molecule identified in C. elegans that mediates recognition of apoptotic cells by cross-linking the PS “eat me” signal with the phagocyte receptor CED-1.

Glycosylation Genes Expressed in Seam Cells Determine Complex Surface Properties and Bacterial Adhesion to the Cuticle of Caenorhabditis elegans

“…As noted above, the br5 allele is a deletion that removes both bus-12 and the adjacent gene ttr-45, so it is probable that the synthetic phenotype is due to an interaction between ttr-45 and a mutation linked to srf-3(e2689), rather than to any allele-specific interaction between srf-3 and bus-12. Very little is known about the function of the ttr gene family in C. elegans, with the exception of a recent report (Wang et al 2010) demonstrating that ttr-52 functions in the recognition of apoptotic cell corpses.…”

Apoptosis-dependent Externalization and Involvement in Apoptotic Cell Clearance of DmCaBP1, an Endoplasmic Reticulum Protein of Drosophila

“…Data obtained from a coimmunoprecipitation experiment and a solid-phase binding assay suggested no physical association between these two proteins (data not shown). Recently, Wang et al (31) reported that a transthyretin-like protein of C. elegans called TTR-52 is secreted from non-apoptotic cells and acts as a bridging molecule between apoptotic cells and phagocytes by binding to phosphatidylserine and CED-1, respectively. As an analogy to this protein, DmCaBP1 could act as a bridging or tethering molecule to promote phagocytosis.…”

Integrin αPS3/βν-mediated Phagocytosis of Apoptotic Cells and Bacteria in Drosophila

“…CED-1 (40,41) and Draper (42,43), a Drosophila counterpart of CED-1, appear to bind proteins in the recognition of apoptotic cells by phagocytes. Draper also recognizes lipoteichoic acid, a cell wall component, as a ligand in the phagocytosis of S. aureus by hemocytes (34), suggesting a multiplicity of ligands for this receptor.…”