title: Novel subcellular locations and functions for secretory pathway Ca2+/Mn2+-ATPases.
abstract: Secretory pathway Ca2+/Mn2+-ATPases (SPCAs) are important for maintenance of cellular Ca2+ and Mn2+ homeostasis, and, to date, all SPCAs have been found to localize to the Golgi apparatus. The single Drosophila SPCA gene (SPoCk) was identified by an in silico screen for novel Ca2+-ATPases. It encoded three SPoCk isoforms with novel, distinct subcellular specificities in the endoplasmic reticulum (ER) and peroxisomes in addition to the Golgi. Furthermore, expression of the peroxisome-associated SPoCk isoform was sexually dimorphic. Overexpression of organelle-specific SPoCk isoforms impacted on cytosolic Ca2+ handling in both cultured Drosophila cells and a transporting epithelium, the Drosophila Malpighian (renal) tubule. Specifically, the ER isoform impacted on inositol-trisphosphate-mediated Ca2+ signaling and the Golgi isoform impacted on diuresis, whereas the peroxisome isoform colocalized with Ca2+ "spherites" and impacted on calcium storage and transport. Interfering RNA directed against the common exons of the three SPoCk isoforms resulted in aberrant Ca2+ signaling and abolished neuropeptide-stimulated diuresis by the tubule. SPoCk thus contributed to both of the contrasting requirements for Ca2+ in transporting epithelia: to transport or store Ca2+ in bulk without compromising its use as a signal.
authors.affiliation: Division of Molecular Genetics, Anderson College Complex, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Tony D
authors.initials: TD
authors.lastname: Southall
authors.forename: Selim
authors.initials: S
authors.lastname: Terhzaz
authors.forename: Pablo
authors.initials: P
authors.lastname: Cabrero
authors.forename: Venkateswara R
authors.initials: VR
authors.lastname: Chintapalli
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Evans
authors.forename: Julian A T
authors.initials: JA
authors.lastname: Dow
authors.forename: Shireen-Anne
authors.initials: SA
authors.lastname: Davies
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004231:Diuresis; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000201:enzymology; D006056:Golgi Apparatus / Q000201:enzymology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008317:Malpighian Tubules / Q000187:drug effects / Q000201:enzymology*; D008345:Manganese / Q000378:metabolism; D020675:Peroxisomes / Q000201:enzymology; D034622:RNA Interference; D014162:Transfection
chemical_list: D029721:Drosophila Proteins; D007527:Isoenzymes; D008345:Manganese; D000252:Calcium-Transporting ATPases; D002118:Calcium