Regulation of Vertebrate Cellular Mg super(2+) Homeostasis by TRPM7

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 exi...

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Bibliographic Details
Published in:Cell 2003-07, Vol.114 (2), p.191-200
Main Authors: Schmitz, C, Perraud, A-L, Johnson, C O, Inabe, K, Smith, M K, Penner, R, Kurosaki, T, Fleig, A, Scharenberg, A M
Format: Article
Language:English
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Summary: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 super(2+). Investigation of the relationship between Mg super(2+) and the cell biological role of TRPM7 revealed that TRPM7-deficient cells become Mg super(2+) deficient, that both the viability and proliferation of TRPM7-deficient cells are rescued by supplementation of extracellular Mg super(2+), and that the capacity of heterologously expressed TRPM7 mutants to complement TRPM7 deficiency correlates with their sensitivity to Mg super(2+). Overall, our results indicate that TRPM7 has a central role in Mg super(2+) homeostasis as a Mg super(2+) uptake pathway regulated through a functional coupling between its channel and kinase domains.
ISSN:0092-8674