1. Defective cortex glia plasma membrane structure underlies light-induced epilepsy in cpes mutants
- Author
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Govind Kunduri, Usha Acharya, Takeshi Bamba, Daniel B. Turner-Evans, Stephen J. Lockett, Kunio Nagashima, Yutaka Konya, Yoshihiro Izumi, Joost C. M. Holthuis, and Jairaj K. Acharya
- Subjects
0301 basic medicine ,Ceramide ,Multidisciplinary ,biology ,biochemical phenomena, metabolism, and nutrition ,Sphingolipid ,Cell biology ,Cell membrane ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,chemistry ,Cortex (anatomy) ,Sphingomyelin synthase ,polycyclic compounds ,biology.protein ,medicine ,Ceramide phosphoethanolamine synthase ,Neuron ,Sphingomyelin - Abstract
Seizures induced by visual stimulation (photosensitive epilepsy; PSE) represent a common type of epilepsy in humans, but the molecular mechanisms and genetic drivers underlying PSE remain unknown, and no good genetic animal models have been identified as yet. Here, we show an animal model of PSE, in Drosophila, owing to defective cortex glia. The cortex glial membranes are severely compromised in ceramide phosphoethanolamine synthase (cpes)-null mutants and fail to encapsulate the neuronal cell bodies in the Drosophila neuronal cortex. Expression of human sphingomyelin synthase 1, which synthesizes the closely related ceramide phosphocholine (sphingomyelin), rescues the cortex glial abnormalities and PSE, underscoring the evolutionarily conserved role of these lipids in glial membranes. Further, we show the compromise in plasma membrane structure that underlies the glial cell membrane collapse in cpes mutants and leads to the PSE phenotype.
- Published
- 2018
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