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Van Goethem, E., Silva, E.A., Xiao, H., Franc, N.C. (2012). The Drosophila TRPP Cation Channel, PKD2 and Dmel/Ced-12 Act in Genetically Distinct Pathways during Apoptotic Cell Clearance.  PLoS ONE 7(2): e31488.
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Research paper

Apoptosis, a genetically programmed cell death, allows for homeostasis and tissue remodelling during development of all multi-cellular organisms. Phagocytes swiftly recognize, engulf and digest apoptotic cells. Yet, to date the molecular mechanisms underlying this phagocytic process are still poorly understood. To delineate the molecular mechanisms of apoptotic cell clearance in Drosophila, we have carried out a deficiency screen and have identified three overlapping phagocytosis-defective mutants, which all delete the fly homologue of the ced-12 gene, known as Dmelced12. As anticipated, we have found that Dmelced-12 is required for apoptotic cell clearance, as for its C. elegans and mammalian homologues, ced-12 and elmo, respectively. However, the loss of Dmelced-12 did not solely account for the phenotypes of all three deficiencies, as zygotic mutations and germ line clones of Dmelced-12 exhibited weaker phenotypes. Using a nearby genetically interacting deficiency, we have found that the polycystic kidney disease 2 gene, pkd2, which encodes a member of the TRPP channel family, is also required for phagocytosis of apoptotic cells, thereby demonstrating a novel role for PKD2 in this process. We have also observed genetic interactions between pkd2, simu, drpr, rya-r44F, and retinophilin (rtp), also known as undertaker (uta), a gene encoding a MORN-repeat containing molecule, which we have recently found to be implicated in calcium homeostasis during phagocytosis. However, we have not found any genetic interaction between Dmelced-12 and simu. Based on these genetic interactions and recent reports demonstrating a role for the mammalian pkd-2 gene product in ER calcium release during store-operated calcium entry, we propose that PKD2 functions in the DRPR/RTP pathway to regulate calcium homeostasis during this process. Similarly to its C. elegans homologue, DmelCed-12 appears to function in a genetically distinct pathway.

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PMC3275576 (PMC) (EuropePMC)
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Correction: The Drosophila TRPP Cation Channel, PKD2 and Dmel/Ced-12 Act in Genetically Distinct Pathways during Apoptotic Cell Clearance.
Van Goethem et al., 2012, PLoS ONE 7(4): [FBrf0219178]

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