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Comments on Victor Venegas et al. (2008) Development & Evolution Meeting "Identification and Characterization of C. elegans CED-1 Mammalian Homologs" (0)
Overview
Victor Venegas, & Zheng Zhou (2008). Identification and Characterization of C. elegans CED-1 Mammalian Homologs presented in Development & Evolution Meeting. Unpublished information; cite only with author permission.
During the development of multicellular organisms, cells undergoing programmed cell death, or apoptosis, are recognized and internalized by other living cells via phagocytosis, a process highly conserved from nematodes to humans. One hundred and thirty-one somatic cells undergo programmed cell death in the C. elegans hermaphrodite. Apoptotic cells present an "eat me" signal in order to be recognized and engulfed by neighboring phagocytes. Under physiological conditions dying cells can be distinguished from living cells using Nomarski Differential Interference Contrast (DIC) microscopy by their refractive button-like appearance. Genetic screens have identified at least eight genes (ced-1, 6, 7, dyn-1 and ced-2, 5, 10, 12) that act within two partially redundant pathways for efficient engulfment of apoptotic cells. CED-1 acts as a phagocytic receptor that recognizes cell corpses and initiates their engulfment. The current understanding of processes that take place during engulfment of dying cells is a receptor mediated model in which a number of pathways and signals play a role. Signaling cascades brought about by receptor interactions lead to various processes required for phagocytosis. The conservation of these mechanisms allows for the identification of putative homologs in the mammalian system. A number of mammalian cell surface receptors have been suggested to act as receptors that recognize cell corpses on the basis of sequence analysis and structure predictions pointing out striking similarities to CED-1, some of these receptors include class-A scavenger receptors (SRA) and low density lipoprotein-related protein 1 (LRP1). In the present study two transmembrane proteins identified by structure prediction, human MEGF10 and mouse Jedi, were characterized in C. elegans. The nematode C. elegans provides a degree of complexity less than that of mammalian systems while maintaining a similar molecular mechanism by which to study human and mouse CED-1 homologs. We provide evidence that transmembrane proteins human MEGF10 and mouse Jedi recognize cell corpses in C. elegans and partially replace CED-1 function.
