The channel-kinase TRPM7 regulates phosphorylation of the translational factor eEF2 via eEF2-k.
Protein translation is an essential but energetically expensive process, which is carefully regulated in accordance to the cellular nutritional and energy status. Eukaryotic elongation factor 2 (eEF2) is a central regulation point since it mediates ribosomal translocation and can be inhibited by phosphorylation at Thr56. TRPM7 is the unique fusion of an ion channel with a functional Ser/Thr-kinase. While TRPM7's channel function has been implicated in regulating vertebrate Mg(2+) uptake required for cell growth, the function of its kinase domain remains unclear. Here, we show that under conditions where cell growth is limited by Mg(2+) availability, TRPM7 via its kinase mediates enhanced Thr56 phosphorylation of eEF2. TRPM7-kinase does not appear to directly phosphorylate eEF2, but rather to influence the amount of eEF2's cognate kinase eEF2-k, involving its phosphorylation at Ser77. These findings suggest that TRPM7's structural duality ensures ideal positioning of its kinase in close proximity to channel-mediated Mg(2+) uptake, allowing for the adjustment of protein translational rates to the availability of Mg(2+).
Integrated Department of Immunology, National Jewish Health and University of Colorado Denver, CO 80206, USA. perrauda@njhealth.org
Anne-Laure
AL
Perraud
Xiaoyun
X
Zhao
Alexey G
AG
Ryazanov
Carsten
C
Schmitz
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology; D002460:Cell Line; D002645:Chickens; D054736:Elongation Factor 2 Kinase / Q000378:metabolism*; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D051379:Mice; D010441:Peptide Chain Elongation, Translational; D020652:Peptide Elongation Factor 2 / Q000378:metabolism*; D010766:Phosphorylation; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases; D011994:Recombinant Proteins / Q000096:biosynthesis; D050053:TRPM Cation Channels / Q000096:biosynthesis / Q000502:physiology*
D020652:Peptide Elongation Factor 2; D011994:Recombinant Proteins; D050053:TRPM Cation Channels; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D054736:Elongation Factor 2 Kinase; D008274:Magnesium