Journal article
Reduced Function of the Glutathione S-Transferase S1 Suppresses Behavioral Hyperexcitability in Drosophila Expressing Mutant Voltage-Gated Sodium Channels
G3 (Bethesda, Md.), Vol.10(4), pp.1327-1340
04/01/2020
DOI: 10.1534/g3.119.401025
PMCID: PMC7144092
PMID: 32054635
Abstract
Voltage-gated sodium (Na
v
) channels play a central role in the generation and propagation of action potentials in excitable cells such as neurons and muscles. To determine how the phenotypes of Na
v
-channel mutants are affected by other genes, we performed a forward genetic screen for dominant modifiers of the seizure-prone, gain-of-function
Dr
osophila melanogaster
Na
v
-channel mutant,
para
Shu
. Our analyses using chromosome deficiencies, gene-specific RNA interference, and single-gene mutants revealed that a null allele of
glutathione S-transferase S1
(
GstS1
) dominantly suppresses
para
Shu
phenotypes. Reduced
GstS1
function also suppressed phenotypes of other seizure-prone Na
v
-channel mutants,
para
GEFS+
and
para
bss
. Notably,
para
Shu
mutants expressed 50% less
GstS1
than wild-type flies, further supporting the notion that
para
Shu
and
GstS1
interact functionally. Introduction of a loss-of-function
GstS1
mutation into a
para
Shu
background led to up- and down-regulation of various genes, with those encoding cytochrome P450 (CYP) enzymes most significantly over-represented in this group. Because
GstS1
is a fly ortholog of mammalian hematopoietic prostaglandin D synthase, and in mammals CYPs are involved in the oxygenation of polyunsaturated fatty acids including prostaglandins, our results raise the intriguing possibility that bioactive lipids play a role in
GstS1
-mediated suppression of
para
Shu
phenotypes.
Details
- Title: Subtitle
- Reduced Function of the Glutathione S-Transferase S1 Suppresses Behavioral Hyperexcitability in Drosophila Expressing Mutant Voltage-Gated Sodium Channels
- Creators
- Hung-Lin Chen - Interdisciplinary Graduate Program in GeneticsJunko Kasuya - Department of Anesthesia, Carver College of MedicinePatrick Lansdon - Interdisciplinary Graduate Program in GeneticsGarrett Kaas - Interdisciplinary Graduate Program in GeneticsHanxi Tang - Iowa Center for Research by Undergraduates, University of Iowa, IA 52242Maggie Sodders - Department of Anesthesia, Carver College of MedicineToshihiro Kitamoto - Interdisciplinary Graduate Program in Genetics
- Resource Type
- Journal article
- Publication Details
- G3 (Bethesda, Md.), Vol.10(4), pp.1327-1340
- DOI
- 10.1534/g3.119.401025
- PMID
- 32054635
- PMCID
- PMC7144092
- NLM abbreviation
- G3 (Bethesda)
- ISSN
- 2160-1836
- eISSN
- 2160-1836
- Publisher
- Genetics Society of America
- Language
- English
- Date published
- 04/01/2020
- Academic Unit
- Iowa Neuroscience Institute; Anesthesia; Neuroscience and Pharmacology
- Record Identifier
- 9984070005202771
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