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PMID:20889130

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Citation

Georgiev, P, Okkenhaug, H, Drews, A, Wright, D, Lambert, S, Flick, M, Carta, V, Martel, C, Oberwinkler, J and Raghu, P (2010) TRPM channels mediate zinc homeostasis and cellular growth during Drosophila larval development. Cell Metab. 12:386-97

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.

Links

PubMed Online version:10.1016/j.cmet.2010.08.012

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:TRPCG

enables

GO:0005385: zinc ion transmembrane transporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:TRPCG

involved_in

GO:0030001: metal ion transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:TRPCG

enables

GO:0022890: inorganic cation transmembrane transporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:TRPCG

part_of

GO:0034703: cation channel complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:TRPCG

involved_in

GO:0055069: zinc ion homeostasis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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