title: TRPM channels mediate zinc homeostasis and cellular growth during Drosophila larval development.
abstract: TRPM channels have emerged as key mediators of diverse physiological functions. However, the ionic permeability relevant to physiological function in vivo remains unclear for most members. We report that the single Drosophila TRPM gene (dTRPM) generates a conductance permeable to divalent cations, especially Zn(2+) and in vivo a loss-of-function mutation in dTRPM disrupts intracellular Zn(2+) homeostasis. TRPM deficiency leads to profound reduction in larval growth resulting from a decrease in cell size and associated defects in mitochondrial structure and function. These phenotypes are cell-autonomous and can be recapitulated in wild-type animals by Zn(2+) depletion. Both the cell size and mitochondrial defect can be rescued by extracellular Zn(2+) supplementation. Thus our results implicate TRPM channels in the regulation of cellular Zn(2+) in vivo. We propose that regulation of Zn(2+) homeostasis through dTRPM channels is required to support molecular processes that mediate class I PI3K-regulated cell growth.
authors.affiliation: Inositide Laboratory, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors.forename: Plamen
authors.initials: P
authors.lastname: Georgiev
authors.affiliation: Inositide Laboratory, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Okkenhaug
authors.affiliation: Emmy Noether Research Group, Experimentelle und Klinische Pharmakologie und Toxikologie, Uniklinikum des Saarlandes, 66421 Homburg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Drews
authors.affiliation: Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge CB2 3AT, UK.
authors.forename: David
authors.initials: D
authors.lastname: Wright
authors.affiliation: Emmy Noether Research Group, Experimentelle und Klinische Pharmakologie und Toxikologie, Uniklinikum des Saarlandes, 66421 Homburg, Germany.
authors.forename: Sachar
authors.initials: S
authors.lastname: Lambert
authors.affiliation: Emmy Noether Research Group, Experimentelle und Klinische Pharmakologie und Toxikologie, Uniklinikum des Saarlandes, 66421 Homburg, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Flick
authors.affiliation: Inositide Laboratory, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors.forename: Valentina
authors.initials: V
authors.lastname: Carta
authors.affiliation: Inositide Laboratory, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors.forename: Cecile
authors.initials: C
authors.lastname: Martel
authors.affiliation: Emmy Noether Research Group, Experimentelle und Klinische Pharmakologie und Toxikologie, Uniklinikum des Saarlandes, 66421 Homburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Oberwinkler
authors.affiliation: Inositide Laboratory, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK. Electronic address: praghu@ncbs.res.in.
authors.forename: Padinjat
authors.initials: P
authors.lastname: Raghu
mesh_terms: D000818:Animals; D048429:Cell Size; D004330:Drosophila / Q000254:growth & development; D006706:Homeostasis; D007814:Larva / Q000254:growth & development*; D008928:Mitochondria / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases; D050053:TRPM Cation Channels / Q000172:deficiency / Q000502:physiology*; D015032:Zinc / Q000172:deficiency / Q000378:metabolism*
chemical_list: D050053:TRPM Cation Channels; D019869:Phosphatidylinositol 3-Kinases; D015032:Zinc