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bioRxiv · 10.1101/2023.09.22.559031

A Complex Containing the Na+/K+ ATPase Regulates Epileptogenesis in Drosophilamelanogaster

Bermudez, S.·Dean, D. M.·Alkin, V.·Wang, Z.·Pham, H.·Kondo, E.·Amini, A.·Deitcher, D. L.
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Abstract

Epileptogenesis, the process through which the brain becomes seizure-prone, is not well understood. Previous work identified a novel gene in Drosophila, julius seizure (jus), that when mutated or developmentally knocked down, leads to epilepsy in adult Drosophila, providing a useful model for dissecting epileptogenesis. Here we report that when a GFP-tagged version of Jus was used as bait in a co-immunoprecipitation (co-IP) assay, a complex of 23 associated proteins was identified that included ATPalpha and Nervana 3, two subunits of the Na+/K+ ATPase. RNAi-mediated knockdown of ATPalpha, Nervana 3, or any of 8 additional complex proteins enhanced seizure susceptibility. The critical period of Jus expression in epileptogenesis was further defined, occurring between pupal stages P4-7; remarkably, the jus seizure phenotype could be rescued by increasing neural activity of jus-expressing neurons during these mid-pupal stages, suggesting that altered neural activity in these neurons may contribute to the seizure phenotype. Our data support a model that, in wild type flies, a protein complex containing Na+/K+ ATPase and Jus prevents epileptogenesis, possibly by regulating neural activity.

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Bermudez, S., Dean, D. M., Alkin, V., Wang, Z., Pham, H., Kondo, E., Amini, A., Deitcher, D. L.. 2023-09-22. A Complex Containing the Na+/K+ ATPase Regulates Epileptogenesis in Drosophilamelanogaster. https://doi.org/10.1101/2023.09.22.559031

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