EFHC1, implicated in juvenile myoclonic epilepsy, functions at the cilium and synapse to modulate dopamine signaling

• DOI: 10.7554/elife.37271
• Publication Date: 2019-02-27T11:01:41Z
• Authors: Catrina M Loucks; Kwangjin Park; Denise S Walker; Andrea H McEwan; Tiffany A Timbers; Evan L Ardiel; Laura J Grundy; Chunmei Li; Jacque-Lynne Johnson; Julie Kennedy; Oliver E Blacque; William Schafer; Catharine H Rankin; Michel R Leroux
• Keywords: Juvenile myoclonic epilepsy; Motile cilium

Neurons throughout the mammalian brain possess non-motile cilia, organelles with varied functions in sensory physiology and cellular signaling. Yet, roles of cilia these neurons are poorly understood. To shed light into their functions, we studied EFHC1, an evolutionarily conserved protein required for motile function linked to a common form inherited epilepsy humans, juvenile myoclonic (JME). We demonstrate that C. elegans EFHC-1 within specialized mechanosensory where it regulates neuronal activation dopamine also localizes at synapse, further modulates signaling cooperation orthologue R-type voltage-gated calcium channel. Our findings unveil previously undescribed dual-regulation excitability sites input (cilium) output (synapse). Such distributed regulatory mechanism may be essential establishing thresholds under physiological conditions, when impaired, represent novel pathomechanism epilepsy.