The cell surface receptor CED-1 mediates apoptotic cell recognition by phagocytic cells, enabling cell corpse clearance in Caenorhabditis elegans. Here, we found that the C. elegans intracellular protein sorting complex, retromer, was required for cell corpse clearance by mediating the recycling of CED-1. Retromer was recruited to the surfaces of phagosomes containing cell corpses, and its loss of function caused defective cell corpse removal. The retromer probably acted through direct interaction with CED-1 in the cell corpse recognition pathway. In the absence of retromer function, CED-1 associated with lysosomes and failed to recycle from phagosomes and cytosol to the plasma membrane. Thus, retromer is an essential mediator of apoptotic cell clearance by regulating phagocytic receptor(s) during cell corpse engulfment.

C. elegans SORF-1 and SORF-2 and their mammalian homologs WDR91 and WDR81 maintain appropriate PtdIns3P levels in early-to-late endosome conversion by forming a complex with the Beclin1 subunit of the PI3K complex.

Platelet-derived growth factors (PDGFs) 1 are major mitogens for connective tissue cells that are involved in diverse biological processes including physiological development, tissue repair, tumorigenesis, and atherosclerosis (1). PDGF family members, PDGF-A, -B, -C, and -D, are assembled as disulfide-linked homo-or heterodimers and exert their activity by binding to and activating specific high affinity cell surface receptors. Two receptor subtypes with protein-tyrosine kinase activity have been identified that can form homo-and heterodimeric receptor complexes: the ␣-subunit, which can bind to the A-, B-, and C-chains of PDGF, and the ␤-subunit, specific for the B-, C-and D-chains (1-4). Dermal fibroblasts are one of the major target cells of PDGF in the initiation and propagation of wound healing in the skin (5). Levels of PDGF receptor (PDGFR)-␣ expression are high in fibroblasts during early embryogenesis, and disruption of PDGFR-␣ results in a reduction in fibroblasts throughout the embryo (6, 7). In contrast, targeted deletion of PDGFR-␤ and analysis of blastocyst chimeras demonstrated no effect of PDGFR-␤ on fibroblast development (8, 9). However, in mice prepared from the blastocyst chimeras that contain a combination of wild-type and PDGFR-␤ Ϫ/Ϫ cells, analysis of granulation tissue formation following the subcutaneous implantation of sponges demonstrated that PDGFR-␤ Ϫ/Ϫ cells were depleted in the granulation tissue (10). These reports suggest that the two subtypes of PDGFR play distinct roles in development and that PDGFR-␤ is important in wound healing by dermal fibroblasts. Analysis of mutant mice in which the cytoplasmic signaling domain of the PDGFR-␤ was used to replace the PDGFR-␣ cytoplasmic domain showed no obvious defects in any of the PDGFR-␣-dependent cell types (11). On the other hand, when the PDGFR-␤ was dependent upon PDGFR-␣ cytoplasmic domain, multiple abnormalities occurred in vascular smooth muscle cell development (11). These data suggest that PDGFR-␤ has unique signaling capacities compared with PDGFR-␣.PDGF binding to the receptors activates a variety of intracellular signaling molecules (12). One of these is phosphatidylinositol 3-kinase (PI3K), which results in the local accumulation of PI(3,4,5)P 3 at the plasma membrane. Synthesized * This study was supported in part by Grants-in-aid for Scientific Research 16390114 and 12470053 from the Ministry of Education, Science, and Culture of Japan. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.§ § To whom correspondence should be addressed: Dept.