In:
eLife, eLife Sciences Publications, Ltd, Vol. 8 ( 2019-02-27)
Kurzfassung:
Neurons throughout the mammalian brain possess non-motile cilia, organelles with varied functions in sensory physiology and cellular signaling. Yet, the roles of cilia 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 EFHC-1 functions within specialized non-motile mechanosensory cilia, where it regulates neuronal activation and dopamine signaling. EFHC-1 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.
Materialart:
Online-Ressource
ISSN:
2050-084X
DOI:
10.7554/eLife.37271.001
DOI:
10.7554/eLife.37271.002
DOI:
10.7554/eLife.37271.003
DOI:
10.7554/eLife.37271.004
DOI:
10.7554/eLife.37271.005
DOI:
10.7554/eLife.37271.006
DOI:
10.7554/eLife.37271.007
DOI:
10.7554/eLife.37271.008
DOI:
10.7554/eLife.37271.009
DOI:
10.7554/eLife.37271.010
DOI:
10.7554/eLife.37271.011
DOI:
10.7554/eLife.37271.012
DOI:
10.7554/eLife.37271.013
DOI:
10.7554/eLife.37271.014
DOI:
10.7554/eLife.37271.015
DOI:
10.7554/eLife.37271.016
DOI:
10.7554/eLife.37271.017
DOI:
10.7554/eLife.37271.018
DOI:
10.7554/eLife.37271.019
DOI:
10.7554/eLife.37271.020
DOI:
10.7554/eLife.37271.024
DOI:
10.7554/eLife.37271.025
Sprache:
Englisch
Verlag:
eLife Sciences Publications, Ltd
Publikationsdatum:
2019
ZDB Id:
2687154-3