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.
N1 - Funding Information:
ACKNOWLEDGMENTS. We thank Vivek Jayaraman for suggesting the experiments on calcium imaging in Drosophila cpes mutants and for providing the expertise and resources for performing the experiments in his laboratory (the Jayaraman laboratory is funded by the Howard Hughes Medical Institute); Dr. Manzoor Bhat for the contactin antibody; and Drs. Shyam Sharan, Ira Daar, Susan Mackem, Mark Lewandoski, and Terry Yamaguchi for comments on the manuscript. This study was funded by the Intramural Division of the National Cancer Institute, NIH, Department of Health and Human Services. U.A. is supported by NIH Grant RO1GM110288. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.
Publisher Copyright:
© 2018 National Academy of Sciences. All rights reserved.
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.
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U2 - 10.1073/pnas.1808463115
DO - 10.1073/pnas.1808463115
M3 - Article
C2 - 30185559
AN - SCOPUS:85053469094
SN - 0027-8424
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
IS - 38
ER -