Undertaker, a Drosophila Junctophilin, links Draper-mediated phagocytosis and calcium homeostasis.
Phagocytosis is important during development and in the immune response for the removal of apoptotic cells and pathogens, yet its molecular mechanisms are poorly understood. In Caenorhabditis elegans, the CED2/5/10/12 pathway regulates actin during phagocytosis of apoptotic cells, whereas the role of the CED1/6/7 pathway in phagocytosis is unclear. We report that Undertaker (UTA), a Drosophila Junctophilin protein, is required for Draper (CED-1 homolog)-mediated phagocytosis. Junctophilins couple Ca2+ channels at the plasma membrane to those of the endoplasmic reticulum (ER), the Ryanodine receptors. We place Draper, its adaptor drCed-6, UTA, the Ryanodine receptor Rya-r44F, the ER Ca2+ sensor dSTIM, and the Ca2+-release-activated Ca2+ channel dOrai in the same pathway that promotes calcium homeostasis and phagocytosis. Thus, our results implicate a Junctophilin in phagocytosis and link Draper-mediated phagocytosis to Ca2+ homeostasis, highlighting a previously uncharacterized role for the CED1/6/7 pathway.
Cuttell
Leigh
L
Medical Research Council Cell Biology Unit, MRC Laboratory for Molecular Cell Biology and Cell and Developmental Biology Department, University College London, Gower Street, London WC1E 6BT, UK.
Vaughan
Andrew
A
Silva
Elizabeth
E
Escaron
Claire J
CJ
Lavine
Mark
M
Van Goethem
Emeline
E
Eid
Jean-Pierre
JP
Quirin
Magali
M
Franc
Nathalie C
NC
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000276:immunology* / Q000378:metabolism; D004625:Embryo, Nonmammalian; D005136:Eye Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D010587:Phagocytosis
D029721:Drosophila Proteins; D005136:Eye Proteins; D008565:Membrane Proteins; C495322:drpr protein, Drosophila; C520357:rtp protein, Drosophila; D002118:Calcium