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Citation
Kroll, J.R., Wong, K.G., Siddiqui, F.M., Tanouye, M.A. (2015). Disruption of Endocytosis with the Dynamin Mutant shibire[ts1] Suppresses Seizures in Drosophila.  Genetics 201(3): 1087--1102.
FlyBase ID
FBrf0230139
Publication Type
Research paper
Abstract

One challenge in modern medicine is to control epilepsies that do not respond to currently available medications. Since seizures consist of coordinated and high-frequency neural activity, our goal was to disrupt neurotransmission with a synaptic transmission mutant and evaluate its ability to suppress seizures. We found that the mutant shibire, encoding dynamin, suppresses seizure-like activity in multiple seizure-sensitive Drosophila genotypes, one of which resembles human intractable epilepsy in several aspects. Because of the requirement of dynamin in endocytosis, increased temperature in the shi(ts1) mutant causes impairment of synaptic vesicle recycling and is associated with suppression of the seizure-like activity. Additionally, we identified the giant fiber neuron as critical in the seizure circuit and sufficient to suppress seizures. Overall, our results implicate mutant dynamin as an effective seizure suppressor, suggesting that targeting or limiting the availability of synaptic vesicles could be an effective and general method of controlling epilepsy disorders.

PubMed ID
PubMed Central ID
PMC4649637 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Genetics
    Title
    Genetics
    Publication Year
    1916-
    ISBN/ISSN
    0016-6731
    Data From Reference
    Aberrations (1)
    Alleles (30)
    Genes (14)
    Human Disease Models (4)
    Natural transposons (1)
    Insertions (3)
    Transgenic Constructs (22)