TRPM Channels Mediate Zinc Homeostasis and Cellular Growth during Drosophila Larval Development

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, e...

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Bibliographic Details
Published in:Cell metabolism 2010-10, Vol.12 (4), p.386-397
Main Authors: Georgiev, Plamen, Okkenhaug, Hanneke, Drews, Anna, Wright, David, Lambert, Sachar, Flick, Melanie, Carta, Valentina, Martel, Cecile, Oberwinkler, Johannes, Raghu, Padinjat
Format: Article
Language:English
Subjects:
Animals
Cell Size
Drosophila - growth & development
Homeostasis
Larva - growth & development
Mitochondria - pathology
Phosphatidylinositol 3-Kinases
TRPM Cation Channels - deficiency
TRPM Cation Channels - physiology
Zinc - deficiency
Zinc - metabolism
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Summary: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 Zn2+ and in vivo a loss-of-function mutation in dTRPM disrupts intracellular Zn2+ 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 Zn2+ depletion. Both the cell size and mitochondrial defect can be rescued by extracellular Zn2+ supplementation. Thus our results implicate TRPM channels in the regulation of cellular Zn2+ in vivo. We propose that regulation of Zn2+ homeostasis through dTRPM channels is required to support molecular processes that mediate class I PI3K-regulated cell growth. ► dTRPM channels are very permeant to Zn2+; dTRPM−/− shows altered Zn2+ homeostasis ► dTRPM−/− have abnormal mitochondrial function and a cell-autonomous growth defect ► dTRPM−/− phenotypes can be recapitulated in wild-type animals by Zn2+ depletion ► dTRPM−/− phenotypes can be rescued by Zn2+ supplementation
ISSN:1550-4131
1932-7420
DOI:10.1016/j.cmet.2010.08.012