Defective cortex glia plasma membrane structure underlies light-induced epilepsy in cpes mutants

Govind Kunduri, Daniel Turner-Evans, Yutaka Konya, Yoshihiro Izumi, Kunio Nagashima, Stephen Lockett, Joost Holthuis, Takeshi Bamba, Usha Acharya, Jairaj K. Acharya

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 glialmembranes. 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.

Original languageEnglish
Pages (from-to)E8919-E8928
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number38
DOIs
Publication statusPublished - Sep 18 2018

Fingerprint

Neuroglia
Epilepsy
Cell Membrane
Light
Drosophila
Animal Models
Reflex Epilepsy
Photic Stimulation
Phosphorylcholine
Sphingomyelins
Ceramides
Genetic Models
Molecular Biology
Seizures
Phenotype
Lipids
Membranes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Defective cortex glia plasma membrane structure underlies light-induced epilepsy in cpes mutants. / Kunduri, Govind; Turner-Evans, Daniel; Konya, Yutaka; Izumi, Yoshihiro; Nagashima, Kunio; Lockett, Stephen; Holthuis, Joost; Bamba, Takeshi; Acharya, Usha; Acharya, Jairaj K.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 38, 18.09.2018, p. E8919-E8928.

Research output: Contribution to journalArticle

Kunduri, Govind ; Turner-Evans, Daniel ; Konya, Yutaka ; Izumi, Yoshihiro ; Nagashima, Kunio ; Lockett, Stephen ; Holthuis, Joost ; Bamba, Takeshi ; Acharya, Usha ; Acharya, Jairaj K. / Defective cortex glia plasma membrane structure underlies light-induced epilepsy in cpes mutants. In: Proceedings of the National Academy of Sciences of the United States of America. 2018 ; Vol. 115, No. 38. pp. E8919-E8928.
@article{f705732ea8b54fec8c6bf781856b2cd1,
title = "Defective cortex glia plasma membrane structure underlies light-induced epilepsy in cpes mutants",
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 glialmembranes. 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.",
author = "Govind Kunduri and Daniel Turner-Evans and Yutaka Konya and Yoshihiro Izumi and Kunio Nagashima and Stephen Lockett and Joost Holthuis and Takeshi Bamba and Usha Acharya and Acharya, {Jairaj K.}",
year = "2018",
month = "9",
day = "18",
doi = "10.1073/pnas.1808463115",
language = "English",
volume = "115",
pages = "E8919--E8928",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "38",

}

TY - JOUR

T1 - Defective cortex glia plasma membrane structure underlies light-induced epilepsy in cpes mutants

AU - Kunduri, Govind

AU - Turner-Evans, Daniel

AU - Konya, Yutaka

AU - Izumi, Yoshihiro

AU - Nagashima, Kunio

AU - Lockett, Stephen

AU - Holthuis, Joost

AU - Bamba, Takeshi

AU - Acharya, Usha

AU - Acharya, Jairaj K.

PY - 2018/9/18

Y1 - 2018/9/18

N2 - 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 glialmembranes. 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.

AB - 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 glialmembranes. 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.

UR - http://www.scopus.com/inward/record.url?scp=85053469094&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053469094&partnerID=8YFLogxK

U2 - 10.1073/pnas.1808463115

DO - 10.1073/pnas.1808463115

M3 - Article

C2 - 30185559

AN - SCOPUS:85053469094

VL - 115

SP - E8919-E8928

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 38

ER -