RRC ID 46306
Author Cunningham KA, Hua Z, Srinivasan S, Liu J, Lee BH, Edwards RH, Ashrafi K.
Title AMP-activated kinase links serotonergic signaling to glutamate release for regulation of feeding behavior in C. elegans.
Journal Cell Metab
Abstract Serotonergic regulation of feeding behavior has been studied intensively, both for an understanding of the basic neurocircuitry of energy balance in various organisms and as a therapeutic target for human obesity. However, its underlying molecular mechanisms remain poorly understood. Here, we show that neural serotonin signaling in C. elegans modulates feeding behavior through inhibition of AMP-activated kinase (AMPK) in interneurons expressing the C. elegans counterpart of human SIM1, a transcription factor associated with obesity. In turn, glutamatergic signaling links these interneurons to pharyngeal neurons implicated in feeding behavior. We show that AMPK-mediated regulation of glutamatergic release is conserved in rat hippocampal neurons. These findings reveal cellular and molecular mediators of serotonergic signaling.
Volume 16(1)
Pages 113-21
Published 2012-7-3
DOI 10.1016/j.cmet.2012.05.014
PII S1550-4131(12)00239-2
PMID 22768843
PMC PMC3413480
MeSH Animals Basic Helix-Loop-Helix Transcription Factors / metabolism Caenorhabditis elegans / cytology Caenorhabditis elegans / enzymology* Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cells, Cultured Chemoreceptor Cells / metabolism Cyclic AMP-Dependent Protein Kinases / metabolism Feeding Behavior* Gastrointestinal Motility Glutamic Acid / metabolism* Hippocampus / cytology Pharynx / innervation Pharynx / metabolism Pharynx / physiology Protein-Serine-Threonine Kinases / genetics Protein-Serine-Threonine Kinases / metabolism* Rats Receptors, Serotonin / metabolism Serotonergic Neurons / enzymology Serotonergic Neurons / metabolism Serotonin / metabolism Synaptic Transmission*
IF 22.415
Times Cited 37
C.elegans tm2877 tm2654 tm1944 tm1325