Ca(2+)-ATPase function is required for intracellular trafficking of the Notch receptor in Drosophila.
Maintaining high Ca(2+) concentrations in the lumen of the endoplasmic reticulum is important for protein synthesis and transport. We identified a lethal complementation group recovered in a screen for mutations that reduce Notch activity as loss-of-function alleles of the Drosophila Ca(2+)-ATPase gene Ca-P60A. Analysis of Ca-P60A mutants indicates that Ca(2+)-ATPase is essential for cell viability and tissue morphogenesis during development. Cultured cells treated with Ca(2+)-ATPase inhibitors exhibit impaired Notch cleavage and receptor trafficking to the cell surface, explaining the genetic interaction between Ca(2+)-ATPase and Notch. Notch and several other transmembrane proteins are mislocalized in tissue clones homozygous for Ca-P60A mutations, demonstrating a general effect on membrane protein trafficking caused by a deficiency in Ca(2+)-ATPase.
Periz
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Department of Genetics, Stellar-Chance Laboratories 709C, University of Pennsylvania School of Medicine, 422 Curie Boulevard, Philadelphia, PA 19104, USA.
Fortini
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D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002460:Cell Line; D007644:Darier Disease / Q000235:genetics; D004330:Drosophila / Q000201:enzymology* / Q000235:genetics; D029721:Drosophila Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017344:Genes, Insect; D005804:Genes, Lethal; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D009154:Mutation; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000378:metabolism; D051880:Receptors, Notch; D015398:Signal Transduction; D019284:Thapsigargin / Q000494:pharmacology; D014162:Transfection
D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D007211:Indoles; D008565:Membrane Proteins; C497759:N protein, Drosophila; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; C000543:cyclopiazonic acid