TY - JOUR TI - EFHC1, implicated in juvenile myoclonic epilepsy, functions at the cilium and synapse to modulate dopamine signaling AU - Loucks, Catrina M AU - Park, Kwangjin AU - Walker, Denise S AU - McEwan, Andrea H AU - Timbers, Tiffany A AU - Ardiel, Evan L AU - Grundy, Laura J AU - Li, Chunmei AU - Johnson, Jacque-Lynne AU - Kennedy, Julie AU - Blacque, Oliver E AU - Schafer, William AU - Rankin, Catharine H AU - Leroux, Michel R A2 - Hobert, Oliver A2 - Westbrook, Gary L VL - 8 PY - 2019 DA - 2019/02/27 SP - e37271 C1 - eLife 2019;8:e37271 DO - 10.7554/eLife.37271 UR - https://doi.org/10.7554/eLife.37271 AB - 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. KW - EFHC1 KW - juvenile myoclonic epilepsy KW - cilia KW - synapse KW - Caenorhabditis elegans JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -