the drosophila trpp cation channel, pkd2 and dmelced-12 act in genetically distinct pathways during apoptotic cell clearance果蝇trpp阳离子通道,pkd2和dmelced-12法案在遗传学上截然不同的途径凋亡细胞间隙.pdf

The Drosophila TRPP Cation Channel, PKD2 and Dmel/ Ced-12 Act in Genetically Distinct Pathways during Apoptotic Cell Clearance 1¤a 1¤b 2 2 Emeline Van Goethem , Elizabeth A. Silva , Hui Xiao , Nathalie C. Franc * 1 Medical Research Council Cell Biology Unit, MRC Laboratory for Molecular Cell Biology and Anatomy and Developmental Biology Department, University College London, London, United Kingdom, 2 The Department of Genetics, Affiliated to the Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, California, United States of America Abstract 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 Dmel\ced12. As anticipated, we have found that Dmel\ced-12 is required for apoptotic cell clearance, as for its C. elegans and mammalian homologues, ced-12 and elmo, respectively. However, the loss of Dmel\ced-12 did not solely account for the phenotypes of all three deficiencies, as zygotic mutations and germ line clones of Dmel\ced-12 exhibited weaker phenotypes. Using a nearby genetically interacting deficiency, we have found that the polycystic kidney disease 2 gene, pkd2, w