Phospholemman, a single-span membrane protein, is an accessory protein of Na,K-ATPase in cerebellum and choroid plexus

Marina S. Feschenko, Claudia Donnet, Randall K. Wetzel, Natalya K. Asinovski, Larry R. Jones, Kathleen J. Sweadner

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

Phospholemman (FXYD1) is a homolog of the Na,K-ATPase γ 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 α subunit isoforms (α1-α3) from cerebellum, indicating that the interaction is not specific to a particular α 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.

Original languageEnglish (US)
Pages (from-to)2161-2169
Number of pages9
JournalJournal of Neuroscience
Volume23
Issue number6
DOIs
StatePublished - Mar 15 2003

Keywords

  • Bergmann glia
  • Cerebellum
  • Choroid plexus
  • FXYD
  • Na,K-ATPase
  • Phospholemman
  • Purkinje cell

ASJC Scopus subject areas

  • Neuroscience(all)

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