Phenotype Distinctions in Mice Deficient in the Neuron-Specific α3 Subunit of Na,K-ATPase: 3 and .

is a Na,K-ATPase gene expressed specifically in neurons in the brain. Human mutations are dominant and produce an unusually wide spectrum of neurological phenotypes, most notably rapid-onset dystonia parkinsonism (RDP) and alternating hemiplegia of childhood (AHC). Here we compared heterozygotes of two mouse lines, a line with little or no expression (3) and a knock-in expressing p.

Na,K-ATPase Expression Can Be Limited Post-Transcriptionally: A Test of the Role of the Beta Subunit, and a Review of Evidence.

The Na,K-ATPase is an α-β heterodimer. It is well known that the Na,K-ATPase β subunit is required for the biosynthesis and trafficking of the α subunit to the plasma membrane. During investigation of properties of human ATP1A3 mutations in 293 cells, we observed a reciprocal loss of endogenous ATP1A1 when expressing ATP1A3.

The FXYD1 protein plays a protective role against pulmonary hypertension and arterial remodeling via redox and inflammatory mechanisms.

Pulmonary hypertension (PH) consists of a heterogenous group of diseases that culminate in increased pulmonary arterial pressure and right ventricular (RV) dysfunction. We sought to investigate the role of FXYD1, a small membrane protein that modulates Na-K-ATPase function, in the pathophysiology of PH. We mined online transcriptome databases to assess FXYD1 expression in PH.

Temperature instability of a mutation at a multidomain junction in Na,K-ATPase isoform ATP1A3 (p.Arg756His) produces a fever-induced neurological syndrome.

ATP1A3 encodes the α3 isoform of Na,K-ATPase. In the brain, it is expressed only in neurons. Human ATP1A3 mutations produce a wide spectrum of phenotypes, but particular syndromes are associated with unique substitutions.

Misfolding, altered membrane distributions, and the unfolded protein response contribute to pathogenicity differences in Na,K-ATPase ATP1A3 mutations.

Missense mutations in ATP1A3, the α3 isoform of Na,K-ATPase, cause neurological phenotypes that differ greatly in symptoms and severity. A mechanistic basis for differences is lacking, but reduction of activity alone cannot explain them. Isogenic cell lines with endogenous α1 and inducible exogenous α3 were constructed to compare mutation properties.