Student Theses and Dissertations

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RU Laboratory

Heintz Laboratory


NKAIN proteins, drosophila NKAIN, neuronal function, membrane excitability


A novel family of Na,K-ATPase interacting (NKAIN) proteins was cloned and characterized. These proteins are highly conserved across species and do not resemble any known proteins in the genome. Aside from the conserved transmembrane domains, NKAINs contain no known functional domains. Striking amino acid conservation in the first two transmembrane domains suggests that the function of these proteins is concentrated in the membrane bilayer. NKAINl, 2, 3 and a splice form of NKAIN4 are brain and testis specific; another splice form of NKAIN4 is expressed ubiquitously. In the central nervous system, NKAINs localize to neurons. The C-terminal tail of NKAIN proteins interacts with the p subunit of the Na,K-ATPase. The Na,K-ATPase pi subunit, NKAINl and another p subunit interacting protein MONaKA form a complex in transfected cells. Since MONaKA shares sequence similarity with the C-terminal part of the Drosophila NKAIN homolog (dNKAIN), it is proposed that dNKAIN function is carried out by two mammalian proteins - NKAIN and MONaKA. Flies with decreased dNKAIN expression show temperature-sensitive seizures, motor deficit and paralysis a phenotype of neuronal hyperexcitability. In contrast, dNKAIN overexpression leads to a phenotype identical to the phenotype of flies with inhibited cellular excitability. Thus, dNKAIN function is likely to decrease membrane excitability, possibly by affecting the Na,K-ATPase function. Neuronal expression of NKAIN proteins and a possible role in membrane excitability strongly suggest that this novel protein family could be critical for neuronal function.


A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy.

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