Gravity force transduced by the MEC-4/MEC-10 DEG/ENaC channel modulates DAF-16/FoxO activity in Caenorhabditis elegans

Nahui Kim, Catherine M. Dempsey, Chih Jen Kuan, Jim V. Zoval, Eyleen O'Rourke, Gary Ruvkun, Marc J. Madou, Ji Ying Sze

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The gravity response is an array of behavioral and physiological plasticity elicited by changes in ambient mechanical force and is an evolutionarily ancient adaptive mechanism. We show in Caenorhabditis elegans that the force of hypergravity is translated into biological signaling via a genetic pathway involving three factors: the degenerin/epithelial Na+ channel (DEG/ENaC) class of mechanosensory channels of touch receptor neurons, the neurotransmitter serotonin, and the FoxO transcription factor DAF-16 known to regulate development, energy metabolism, stress responses, and aging. After worms were exposed to hypergravity for 3 hr, their muscular and neuronal functions were preserved, but they exhibited DAF-16::GFP nuclear accumulation in cells throughout the body and accumulated excess fat. Mutations in MEC-4/MEC-10 DEG/ENaC or its partners MEC-6, MEC-7, and MEC-9 blocked DAF-16::GFP nuclear accumulation induced by hypergravity but did not affect DAF-16 response to other stresses. We show that exogenous serotonin and the antidepressant fluoxetine can attenuate DAF-16::GFP nuclear accumulation in WT animals exposed to hypergravity. These results reveal a novel physiological role of the mechanosensory channel, showing that the perception of mechanical stress controls FoxO signaling pathways and that inactivation of DEG/ENaC may decouple mechanical loading and physiological responses.

Original languageEnglish (US)
Pages (from-to)835-845
Number of pages11
JournalGenetics
Volume177
Issue number2
DOIs
StatePublished - Oct 2007

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Degenerin Sodium Channels
Hypergravity
Epithelial Sodium Channels
Caenorhabditis elegans
Gravitation
Serotonin
Mechanical Stress
Neurotransmitter Receptor
Fluoxetine
Touch
Energy Metabolism
Antidepressive Agents
Transcription Factors
Fats
Neurons
Mutation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Gravity force transduced by the MEC-4/MEC-10 DEG/ENaC channel modulates DAF-16/FoxO activity in Caenorhabditis elegans. / Kim, Nahui; Dempsey, Catherine M.; Kuan, Chih Jen; Zoval, Jim V.; O'Rourke, Eyleen; Ruvkun, Gary; Madou, Marc J.; Sze, Ji Ying.

In: Genetics, Vol. 177, No. 2, 10.2007, p. 835-845.

Research output: Contribution to journalArticle

Kim, Nahui ; Dempsey, Catherine M. ; Kuan, Chih Jen ; Zoval, Jim V. ; O'Rourke, Eyleen ; Ruvkun, Gary ; Madou, Marc J. ; Sze, Ji Ying. / Gravity force transduced by the MEC-4/MEC-10 DEG/ENaC channel modulates DAF-16/FoxO activity in Caenorhabditis elegans. In: Genetics. 2007 ; Vol. 177, No. 2. pp. 835-845.
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