Gravity force transduced by the MEC-4/MEC-10 DEG/ENaC channel modulates DAF-16/FoxO activity in Caenorhabditis elegans.
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.
Kim
Nahui
N
Interdisciplinary Materials Science and Engineering, University of California, Irvine, California 92697, USA.
Dempsey
Catherine M
CM
Kuan
Chih-Jen
CJ
Zoval
Jim V
JV
O'Rourke
Eyleen
E
Ruvkun
Gary
G
Madou
Marc J
MJ
Sze
Ji Y
JY
D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D053503:Epithelial Sodium Channels / Q000502:physiology*; D051858:Forkhead Transcription Factors; D006112:Gravitation; D008465:Mechanoreceptors / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology*; D013314:Stress, Mechanical; D014157:Transcription Factors / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; C094927:Deg-1 protein, C elegans; D053503:Epithelial Sodium Channels; D051858:Forkhead Transcription Factors; C115871:Mec-4 protein, C elegans; D008565:Membrane Proteins; D015222:Sodium Channels; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C085942:MEC-10 protein, C elegans