What question did this study set out to answer?

To characterize the functional and structural consequences of a novel de novo C-terminal ATP1A3 mutation identified in a patient with rapid-onset dystonia-parkinsonism.

April 7, 2009Human Molecular Genetics

A C-terminal mutation of ATP1A3 underscores the crucial role of sodium affinity in the pathophysiology of rapid-onset dystonia-parkinsonism

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Authors

PBPatricia BlancoUniversidade da Coruña AEAnja P. EinholmAarhus University HMHafsa MamsaUniversity of California, Los Angeles

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Implication

Functional genetic analysis reveals impaired sodium affinity from a novel ATP1A3 mutation in a dystonia patient, highlighting the C-terminus role in disease pathophysiology.

Key Points

To characterize the functional and structural consequences of a novel de novo C-terminal ATP1A3 mutation identified in a patient with rapid-onset dystonia-parkinsonism.
Identified a de novo in-frame tyrosine insertion at the C terminus of the Na+/K+-ATPase alpha3-subunit in a single patient with rapid-onset dystonia-parkinsonism.
Evaluated mutant protein expression, plasma membrane trafficking, and cell survival under ouabain challenge in vitro.
Conducted functional kinetic measurements of sodium affinity alongside structural modeling of E1 and E2 enzyme conformations.
Mutant alpha3-subunits exhibited normal biogenesis and plasma membrane targeting, but cells expressing the mutation demonstrated reduced survival during ouabain exposure.
Functional analysis revealed a drastic reduction in Na+ affinity associated with the strategic positioning of the C terminus adjacent to the third Na+ binding site.

Cite This Study

Blanco et al. (2009) studied this question.

synapsesocial.com/papers/6aaf9b24327e2162f5d0720e https://doi.org/10.1093/hmg/ddp170

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Implication

Functional genetic analysis reveals impaired sodium affinity from a novel ATP1A3 mutation in a dystonia patient, highlighting the C-terminus role in disease pathophysiology.

A C-terminal mutation of ATP1A3 underscores the crucial role of sodium affinity in the pathophysiology of rapid-onset dystonia-parkinsonism

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Implication

Key Points

Cite This Study

A C-terminal mutation of ATP1A3 underscores the crucial role of sodium affinity in the pathophysiology of rapid-onset dystonia-parkinsonism

Discussion

Member takes

Implication

Key Points

Cite This Study

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