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Data from: EFHC1, implicated in juvenile myoclonic epilepsy, functions at the cilium and synapse to modulate dopamine signaling Loucks, Catrina M.; Park, Kwangjin; Walker, Denise S.; McEwan, Andrea H.; Timbers, Tiffany A.; Ardiel, Evan L.; Grundy, Laura J.; Li, Chunmei; Johnson, Jacque-Lynne; Kennedy, Julie; Blacque, Oliver E.; Schafer, William R.; Rankin, Catharine H.; Leroux, Michel R.

Description

Abstract
Neurons throughout the mammalian brain possess non-motile cilia, organelles with varied functions in sensory physiology and cellular signaling, yet their roles in these neurons are poorly understood. To shed light into their functions, we studied EFHC1, an evolutionarily conserved protein required for motile cilia function and linked to a common form of inherited epilepsy in humans, juvenile myoclonic epilepsy (JME). We demonstrate that C. elegans EFHC1 functions within specialized non-motile mechanosensory cilia, where it regulates neuronal activation and dopamine signaling. EFHC1 also localizes at the synapse, where it further modulates dopamine signaling in cooperation with the orthologue of an R-type voltage-gated calcium channel. Our findings unveil a previously undescribed dual-regulation of neuronal excitability at sites of neuronal sensory input (cilium) and neuronal output (synapse). Such a distributed regulatory mechanism may be essential for establishing neuronal activation thresholds under physiological conditions, and when impaired, may represent a novel pathomechanism for epilepsy.
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EFHC1-data_2019-02-04

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Title
Data from: EFHC1, implicated in juvenile myoclonic epilepsy, functions at the cilium and synapse to modulate dopamine signaling
Creator
Loucks, Catrina M.; Park, Kwangjin; Walker, Denise S.; McEwan, Andrea H.; Timbers, Tiffany A.; Ardiel, Evan L.; Grundy, Laura J.; Li, Chunmei; Johnson, Jacque-Lynne; Kennedy, Julie; Blacque, Oliver E.; Schafer, William R.; Rankin, Catharine H.; Leroux, Michel R.
Date Issued
2021-05-19
Description
Abstract
Neurons throughout the mammalian brain possess non-motile cilia, organelles with varied functions in sensory physiology and cellular signaling, yet their roles in these neurons are poorly understood. To shed light into their functions, we studied EFHC1, an evolutionarily conserved protein required for motile cilia function and linked to a common form of inherited epilepsy in humans, juvenile myoclonic epilepsy (JME). We demonstrate that C. elegans EFHC1 functions within specialized non-motile mechanosensory cilia, where it regulates neuronal activation and dopamine signaling. EFHC1 also localizes at the synapse, where it further modulates dopamine signaling in cooperation with the orthologue of an R-type voltage-gated calcium channel. Our findings unveil a previously undescribed dual-regulation of neuronal excitability at sites of neuronal sensory input (cilium) and neuronal output (synapse). Such a distributed regulatory mechanism may be essential for establishing neuronal activation thresholds under physiological conditions, and when impaired, may represent a novel pathomechanism for epilepsy.; Usage notes
EFHC1-data_2019-02-04
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Notes

Dryad version number: 1

Version status: submitted

Dryad curation status: Published

Sharing link: https://datadryad.org/stash/share/ZGy8EkCEDZgqqRJWL2cZOKGq3Qf2pUzanilhKUK73HQ</p>

Storage size: 81790293

Visibility: public
Date Available
2020-06-24
Provider
University of British Columbia Library
License
CC0 1.0
DOI
10.14288/1.0397781
URI
https://doi.org/10.5683/SP2/LBJ5HF
Publisher DOI
https://doi.org/10.5683/SP2/LBJ5HF; https://doi.org/10.5061/dryad.bb46h5s
Rights URI
http://creativecommons.org/publicdomain/zero/1.0
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CC0 1.0