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Previous Article | Next Article
The Journal of Neuroscience, February 15, 2003, 23(4):1276
Neural Dysfunction and Neurodegeneration in Drosophila Na+/K+ ATPase Alpha Subunit Mutants
Michael J. Palladino, Jill E. Bower, Robert Kreber, and Barry Ganetzky Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
The Na+/K+ ATPase asymmetrically distributes sodium and potassium ions across the plasma membrane to generate and maintain the membrane potential in many cell types. Although these pumps have been hypothesized to be involved in various human neurological disorders, including seizures and neurodegeneration, direct genetic evidence has been lacking. Here, we describe novel mutations in the Drosophila gene encoding the
(catalytic) subunit of the Na+/K+ ATPase that lead to behavioral abnormalities, reduced life span, and severe neuronal hyperexcitability. These phenotypes parallel the occurrence of extensive, age-dependent neurodegeneration. We have also discovered that the ATPalpha transcripts undergo alternative splicing that substantially increases the diversity of potential proteins. Our data show that maintenance of neuronal viability is dependent on normal sodium pump activity and establish Drosophila as a useful model for investigating the role of the pump in human neurodegenerative and seizure disorders.
Key words: neuropathology; paralysis; hyperexcitability; excitotoxicity; alternative splicing; ATPalpha; Na/K ATPase; neurodegeneration
Copyright © 2003 Society for Neuroscience 0270-6474/03/2341276-11$05.00/0
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