Impaired routing of wild type FXYD2 after oligomerisation with FXYD2-G41R might explain the dominant nature of renal hypomagnesemia.
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SourceBiochimica et Biophysica Acta. Biomembranes, 1778, 2, (2008), pp. 398-404
Article / Letter to editor
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Biochimica et Biophysica Acta. Biomembranes
SubjectIGMD 5: Health aging / healthy living; IGMD 8: Mitochondrial medicine; IGMD 9: Renal disorder; N4i 1: Pathogenesis and modulation of inflammation; N4i 3: Poverty-related infectious diseases; NCMLS 2: Metabolism, transport and motion; NCMLS 4: Energy and redox metabolism; NCMLS 5: Membrane transport and intracellular motility; UMCN 5.1: Genetic defects of metabolism; UMCN 5.4: Renal disorders
Autosomal dominant renal hypomagnesemia, associated with hypocalciurea, has been linked to a G to A mutation at nucleotide position 121 in the FXYD2 gene, resulting in the substitution of Gly with Arg at residue 41 of the protein. FXYD2, also called the Na,K-ATPase gamma-subunit, binds to Na,K-ATPase and influences its cation affinities. In this paper, we provide evidence for the molecular mechanism underlying the dominant character of the disorder. Co-immunoprecipitation experiments using tagged FXYD2 proteins demonstrated that wild type FXYD2 proteins oligomerise. Moreover, FXYD2-G41R also shows oligomerisation with itself and with the wild type protein. In the case of FXYD2-G41R, however, formation of homo-oligomers was prevented by addition of DTT or introduction of the C52A mutation. Finally, we demonstrated that artificial glycosylation of the wild type FXYD2 is reduced when co-expressed with FXYD2-G41R. These data indicate that binding of FXYD2-G41R to wild type FXYD2 subunit might abrogate the routing of wild type FXYD2 to the plasma membrane thus causing the dominant nature of this mutation.
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