Phospholemman, a Single-Span Membrane Protein, Is an Accessory Protein of Na,K-ATPase in Cerebellum and Choroid Plexus

Phospholemman (FXYD1) is a homolog of the Na,K-ATPase gamma subunit (FXYD2), a small accessory protein that modulates ATPase activity. Here we show that phospholemman is highly expressed in selected structures in the CNS. It is most abundant in cerebellum, where it was detected in the molecular laye...

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Bibliographic Details
Published in:The Journal of neuroscience 2003-03, Vol.23 (6), p.2161-2169
Main Authors: Feschenko, Marina S, Donnet, Claudia, Wetzel, Randall K, Asinovski, Natalya K, Jones, Larry R, Sweadner, Kathleen J
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Antibodies - pharmacology
Blotting, Western
Brain - metabolism
Cattle
Cell Membrane - chemistry
Cerebellum - chemistry
Cerebellum - metabolism
Choroid Plexus - chemistry
Choroid Plexus - metabolism
Enzyme Activation - drug effects
Humans
Membrane Proteins - chemistry
Membrane Proteins - metabolism
Mice
Molecular Sequence Data
Phosphoproteins - chemistry
Phosphoproteins - metabolism
Precipitin Tests
Protein Binding - physiology
Protein Isoforms - chemistry
Protein Isoforms - metabolism
Purkinje Cells - metabolism
Rats
Sequence Alignment
Sodium-Potassium-Exchanging ATPase - chemistry
Sodium-Potassium-Exchanging ATPase - metabolism
Subcellular Fractions - chemistry
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Summary:Phospholemman (FXYD1) is a homolog of the Na,K-ATPase gamma subunit (FXYD2), a small accessory protein that modulates ATPase activity. Here we show that phospholemman is highly expressed in selected structures in the CNS. It is most abundant in cerebellum, where it was detected in the molecular layer, in Purkinje neurons, and in axons traversing the granule cell layer. Phospholemman was particularly enriched in choroid plexus, the organ that secretes CSF in the ventricles, where it colocalized with Na,K-ATPase in the apical membrane. It was also enriched, with Na,K-ATPase, in certain tanycytes or ependymal cells of the ventricle wall. Two different experimental approaches demonstrated that phospholemman physically associated with the Na,K-ATPase in cerebellum and choroid plexus: the proteins copurified after detergent treatment and co-immunoprecipitated from solubilized crude membranes using either anti-phospholemman or anti-Na,K-ATPase antibodies. Phospholemman antibodies precipitated all three Na,K-ATPase alpha subunit isoforms (alpha1-alpha3) from cerebellum, indicating that the interaction is not specific to a particular alpha isoform and consistent with the presence of phospholemman in both neurons and glia. Antibodies against the C-terminal domain of phospholemman reduced Na,K-ATPase activity in vitro without effect on Na+ affinity. At least two other FXYD family members have been detected in the CNS, suggesting that additional complexity of sodium pump regulation will be found.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.23-06-02161.2003