GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:19884312

From GONUTS
Jump to: navigation, search
Citation

Hekmat-Scafe, DS, Mercado, A, Fajilan, AA, Lee, AW, Hsu, R, Mount, DB and Tanouye, MA (2010) Seizure sensitivity is ameliorated by targeted expression of K+-Cl- cotransporter function in the mushroom body of the Drosophila brain. Genetics 184:171-83

Abstract

The kcc(DHS1) allele of kazachoc (kcc) was identified as a seizure-enhancer mutation exacerbating the bang-sensitive (BS) paralytic behavioral phenotypes of several seizure-sensitive Drosophila mutants. On their own, young kcc(DHS1) flies also display seizure-like behavior and demonstrate a reduced threshold for seizures induced by electroconvulsive shock. The product of kcc shows substantial homology to KCC2, the mammalian neuronal K(+)-Cl(-) cotransporter. The kcc(DHS1) allele is a hypomorph, and its seizure-like phenotype reflects reduced expression of the kcc gene. We report here that kcc functions as a K(+)-Cl(-) cotransporter when expressed heterologously in Xenopus laevis oocytes: under hypotonic conditions that induce oocyte swelling, oocytes that express Drosophila kcc display robust ion transport activity observed as a Cl(-)-dependent uptake of the K(+) congener (86)Rb(+). Ectopic, spatially restricted expression of a UAS-kcc(+) transgene was used to determine where cotransporter function is required in order to rescue the kcc(DHS1) BS paralytic phenotype. Interestingly, phenotypic rescue is largely accounted for by targeted, circumscribed expression in the mushroom bodies (MBs) and the ellipsoid body (EB) of the central complex. Intriguingly, we observed that MB induction of kcc(+) functioned as a general seizure suppressor in Drosophila. Drosophila MBs have generated considerable interest especially for their role as the neural substrate for olfactory learning and memory; they have not been previously implicated in seizure susceptibility. We show that kcc(DHS1) seizure sensitivity in MB neurons acts via a weakening of chemical synaptic inhibition by GABAergic transmission and suggest that this is due to disruption of intracellular Cl(-) gradients in MB neurons.

Links

PubMed PMC2815914 Online version:10.1534/genetics.109.109074

Keywords

Animals; Behavior, Animal; Brain/cytology; Brain/metabolism; Brain/physiology; Disease Susceptibility/metabolism; Drosophila melanogaster/cytology; Drosophila melanogaster/metabolism; Drosophila melanogaster/physiology; Electrophysiological Processes; Female; Gene Expression; Humans; Insect Proteins/genetics; Insect Proteins/metabolism; Male; Mushroom Bodies/cytology; Mushroom Bodies/metabolism; Mushroom Bodies/physiology; Neuronal Plasticity/genetics; Phenotype; Seizures/genetics; Symporters/genetics; Symporters/metabolism; Synapses/metabolism; Synaptic Transmission; Xenopus laevis/genetics; gamma-Aminobutyric Acid/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:A0A0B4LGD3

enables

GO:0015379: potassium:chloride symporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:A0A0B4LHE0

enables

GO:0015379: potassium:chloride symporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:Q8MKK5

enables

GO:0015379: potassium:chloride symporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:Q8MLQ5

enables

GO:0015379: potassium:chloride symporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:Q9W1G5

enables

GO:0015379: potassium:chloride symporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:Q9W1G6

enables

GO:0015379: potassium:chloride symporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.