A homolog of FHM2 is involved in modulation of excitatory neurotransmission by serotonin in C. elegans

Elena G. Govorunova, Mustapha Moussaif, Andrey Kullyev, Ken C.Q. Nguyen, Thomas V. Mcdonald, David H. Hall, Ji Y. Sze

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The C. elegans eat-6 gene encodes a Na+, K+-ATPase α subunit and is a homolog of the familial hemiplegic migraine candidate gene FHM2. Migraine is the most common neurological disorder linked to serotonergic dysfunction. We sought to study the pathophysiological mechanisms of migraine and their relation to serotonin (5-HT) signaling using C. elegans as a genetic model. In C. elegans, exogenous 5-HT inhibits paralysis induced by the acetylcholinesterase inhibitor aldicarb. We show that eat-6 is expressed in ventral cord ACh motor neurons, and that cell-specific RNAi of eat-6 in the ACh neurons leads to hypersensitivity to aldicarb. Electron microscopy showed an increased number of synaptic vesicles in the ACh neurons in the eat-6(ad467) mutant. Genetic analyses suggest that EAT-6 interacts with EGL-30 Gaq, EGL-8 phospholipase C and SLO-1 BK channel signaling to modulate ACh neurotransmission and that either reduced or excessive EAT-6 function may lead to increased ACh neurotransmission. Study of the interaction between eat-6 and 5-HT receptors revealed both stimulatory and inhibitory 5-HT inputs to the NMJs. We show that the inhibitory and stimulatory 5-HT signals arise from distinct 5-HT neurons. The role of eat-6 in modulation of excitatory neurotransmission by 5-HT may provide a genetic explanation for the therapeutic effects of the drugs targeting 5-HT receptors in the treatment of migraine patients.

Original languageEnglish (US)
Article numbere10368
JournalPloS one
Volume5
Issue number4
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • General

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