ABSTRACT
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.
Subject(s)
Calcium/metabolism , Drosophila Proteins/metabolism , Drosophila melanogaster/immunology , Membrane Proteins/metabolism , Phagocytosis , Animals , Animals, Genetically Modified , Apoptosis , Drosophila melanogaster/metabolism , Embryo, Nonmammalian , Eye ProteinsABSTRACT
BACKGROUND: Mammalian STIM1 and STIM2 and the single Drosophila homologue dSTIM have been identified as key regulators of store-operated Ca2+ entry in cells. STIM proteins function both as molecular sensors of Ca2+concentration in the endoplasmic reticulum (ER) and the molecular triggers that activate SOC channels in the plasma membrane. Ca2+ is a crucial intracellular messenger utilised in many cellular processes, and regulators of Ca2+ homeostasis in the ER and cytosol are likely to play important roles in developmental processes. STIM protein expression is altered in several tumour types but the role of these proteins in developmental signalling pathways has not been thoroughly examined. RESULTS: We have investigated the expression and developmental function of dSTIM in Drosophila and shown that dSTIM is widely expressed in embryonic and larval tissues. Using the UAS-Gal4 induction system, we have expressed full-length dSTIM protein and a dsRNAi construct in different tissues. We demonstrate an essential role for dSTIM in larval development and survival, and a tissue-specific role in specification of mechanosensory bristles in the notum and specification of wing vein thickness. CONCLUSION: Our studies show that dSTIM regulates growth and patterning of imaginal discs and indicate potential interactions with the Notch and Wingless signaling pathways. These interactions may be relevant to studies implicating STIM family proteins in tumorigenesis.
