title: Regulation of vertebrate cellular Mg2+ homeostasis by TRPM7.
abstract: TRPM7 is a polypeptide with intrinsic ion channel and protein kinase domains whose targeted deletion causes cells to experience growth arrest within 24 hr and eventually die. Here, we show that while TRPM7's kinase domain is not essential for activation of its channel, a functional coupling exists such that structural alterations of the kinase domain alter the sensitivity of channel activation to Mg(2+). Investigation of the relationship between Mg(2+) and the cell biological role of TRPM7 revealed that TRPM7-deficient cells become Mg(2+) deficient, that both the viability and proliferation of TRPM7-deficient cells are rescued by supplementation of extracellular Mg(2+), and that the capacity of heterologously expressed TRPM7 mutants to complement TRPM7 deficiency correlates with their sensitivity to Mg(2+). Overall, our results indicate that TRPM7 has a central role in Mg(2+) homeostasis as a Mg(2+) uptake pathway regulated through a functional coupling between its channel and kinase domains.
authors.affiliation: Department of Pediatrics, University of Washington and Children's Hospital and Regional Medical Center, Seattle, WA 98195, USA.
authors.forename: Carsten
authors.initials: C
authors.lastname: Schmitz
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Perraud
authors.forename: Catherine O
authors.initials: CO
authors.lastname: Johnson
authors.forename: Kazunori
authors.initials: K
authors.lastname: Inabe
authors.forename: Megan K
authors.initials: MK
authors.lastname: Smith
authors.forename: Reinhold
authors.initials: R
authors.lastname: Penner
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
authors.forename: Andrea
authors.initials: A
authors.lastname: Fleig
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Scharenberg
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D015971:Gene Expression Regulation, Enzymologic; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology / Q000502:physiology*; D010770:Phosphotransferases / Q000378:metabolism; D017354:Point Mutation; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D017384:Sequence Deletion; D014162:Transfection
chemical_list: D007473:Ion Channels; D000255:Adenosine Triphosphate; D010770:Phosphotransferases; D011494:Protein Kinases; D008274:Magnesium