A Complex Containing the Na<sup>+</sup>/K<sup>+</sup>ATPase Regulates Epileptogenesis in<i>Drosophila melanogaster</i>
Abstract Epileptogenesis, the process through which the brain becomes seizure-prone, is not well understood. Previous work identified a novel gene inDrosophila,julius seizure(jus), that when mutated or developmentally knocked down, leads to epilepsy in adultDrosophila, 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, thejusseizure phenotype could be rescued by increasing neural activity ofjus-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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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 27. Sept. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bermudez, Sarah [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2023.09.22.559031 |
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| PPN (Katalog-ID): |
XBI040975290 |
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| 520 | |a Abstract Epileptogenesis, the process through which the brain becomes seizure-prone, is not well understood. Previous work identified a novel gene inDrosophila,julius seizure(jus), that when mutated or developmentally knocked down, leads to epilepsy in adultDrosophila, 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, thejusseizure phenotype could be rescued by increasing neural activity ofjus-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. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
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| 700 | 1 | |a Dean, Derek M. |0 (orcid)0000-0002-8599-773X |4 aut | |
| 700 | 1 | |a Alkin, Victoria |4 aut | |
| 700 | 1 | |a Wang, Ziming |4 aut | |
| 700 | 1 | |a Pham, Huy |4 aut | |
| 700 | 1 | |a Kondo, Emily |4 aut | |
| 700 | 1 | |a Amini, Andrew |4 aut | |
| 700 | 1 | |a Deitcher, David L. |0 (orcid)0000-0002-8512-8868 |4 aut | |
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