Na,K-ATPase from mice lacking the subunit (FXYD2) exhibits altered Na affinity and decreased thermal stability

Jones, D. Holstead, Li, Tony Y., Arystarkhova, Elena, Barr, Kevin J., Wetzel, Randall K., Peng, Jun, Markham, Kathryn, Sweadner, Kathleen J., Fong, Guo-Hua and Kiddera, Gerald M. (2005) Na,K-ATPase from mice lacking the subunit (FXYD2) exhibits altered Na affinity and decreased thermal stability. The Journal of Biological Chemistry, 280 19: 19003-19011. doi:10.1074/jbc.M500697200

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Author Jones, D. Holstead
Li, Tony Y.
Arystarkhova, Elena
Barr, Kevin J.
Wetzel, Randall K.
Peng, Jun
Markham, Kathryn
Sweadner, Kathleen J.
Fong, Guo-Hua
Kiddera, Gerald M.
Title Na,K-ATPase from mice lacking the subunit (FXYD2) exhibits altered Na affinity and decreased thermal stability
Formatted title
Na,K-ATPase from mice lacking the γ subunit (FXYD2) exhibits
altered Na+ affinity and decreased thermal stability
Journal name The Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2005-03-08
Sub-type Article (original research)
DOI 10.1074/jbc.M500697200
Open Access Status File (Publisher version)
Volume 280
Issue 19
Start page 19003
End page 19011
Total pages 9
Place of publication United States
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Subject 0605 Microbiology
Formatted abstract
The γ subunit of the Na,K-ATPase, a 7-kDa single-span membrane protein, is a member of the FXYD gene family. Several FXYD proteins have been shown to bind to  Na,K-ATPase and modulate its properties, and each FXYD protein appears to alter enzyme kinetics differently. Different results have sometimes been obtained with different experimental systems, however. To test for effects of γ in a native tissue environment, mice lacking a functional γ subunit gene (Fxyd2) were generated. These  mice were viable and without observable pathology. Prior work in the mouse embryo  showed that γ is expressed at the blastocyst stage. However, there was no delay in  blastocele formation, and the expected Mendelian ratios of offspring were obtained  even with Fxyd2-/- dams. In adult Fxyd2-/- mouse kidney, splice variants of γ that have  different nephron segment-specific expression patterns were absent. Purified  γ-deficient renal Na,K-ATPase displayed higher apparent affinity for Na+ without  significant change in apparent affinity for K+. Affinity for ATP, which was expected to be decreased, was instead slightly increased. The results suggest that regulation of  Na+ sensitivity is a major functional role for this protein, whereas regulation of ATP affinity  may be context-specific. Most importantly, this implies that γ and other  FXYD proteins  have their effects by local and not global conformation change.  Na,K-ATPase lacking  the γ subunit had increased thermal lability. Combined with  other evidence that γ  participates in an early step of thermal denaturation, this  indicates that FXYD proteins  may play an important structural role in the enzyme  complex.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
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Created: Thu, 07 Jan 2010, 15:55:37 EST by Simon Utteridge on behalf of School of Biomedical Sciences