Ca2+-ATPase function is required for intracellular trafficking of the Notch receptor in Drosophila

Maintaining high Ca2+ 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 Ca2+-ATPase gene Ca-P60A, Analysis of Ca-P60A mutants indicates that Ca2+-ATPase is essential for cell viability and tissue morphogenesis during development. Cultured cells treated with Ca2+-ATPase inhibitors exhibit impaired Notch cleavage and receptor trafficking to the cell surface, explaining the genetic interaction between Ca2+-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 Ca2+-ATPase.