LTRPC7 is a Mg.ATP-regulated divalent cation channel required for cell viability.
The molecular mechanisms that regulate basal or background entry of divalent cations into mammalian cells are poorly understood. Here we describe the cloning and functional characterization of a Ca2+- and Mg2+-permeable divalent cation channel, LTRPC7 (nomenclature compatible with that proposed in ref. 1), a new member of the LTRPC family of putative ion channels. Targeted deletion of LTRPC7 in DT-40 B cells was lethal, indicating that LTRPC7 has a fundamental and nonredundant role in cellular physiology. Electrophysiological analysis of HEK-293 cells overexpressing recombinant LTRPC7 showed large currents regulated by millimolar levels of intracellular Mg.ATP and Mg.GTP with the permeation properties of a voltage-independent divalent cation influx pathway. Analysis of several cultured cell types demonstrated small magnesium-nucleotide-regulated metal ion currents (MagNuM) with regulation and permeation properties essentially identical to the large currents observed in cells expressing recombinant LTRPC7. Our data indicate that LTRPC7, by virtue of its sensitivity to physiological Mg.ATP levels, may be involved in a fundamental process that adjusts plasma membrane divalent cation fluxes according to the metabolic state of the cell.
Nadler
M J
MJ
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Hermosura
M C
MC
Inabe
K
K
Perraud
A L
AL
Zhu
Q
Q
Stokes
A J
AJ
Kurosaki
T
T
Kinet
J P
JP
Penner
R
R
Scharenberg
A M
AM
Fleig
A
A
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D002645:Chickens; D003001:Cloning, Molecular; D018390:Gene Targeting; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D050053:TRPM Cation Channels
D007473:Ion Channels; D008565:Membrane Proteins; D050053:TRPM Cation Channels; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D011494:Protein Kinases; C421903:Trpm7 protein, mouse; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human