Melatonin signaling regulates locomotion behavior and homeostatic states through distinct receptor pathways in Caenorhabditis elegans.
Melatonin is a hormone that controls circadian rhythms and seasonal behavioral changes in vertebrates. Recent studies indicate that melatonin participates in diverse physiological functions including the modulation of neural activities. Melatonin is also detected in many other organisms that do not exhibit obvious circadian rhythms, but their precise functions are not known. To understand the role of melatonin and its genetic pathway in vivo, we examined the effects of melatonin and its receptor antagonists on various behaviors in Caenorhabditis elegans. Exogenously applied melatonin specifically decreased locomotion rates in 15-min treatments, suggesting that melatonin directly regulates neural activities for locomotion. This melatonin signaling functions through MT1-like melatonin receptors, because the MT1/2 receptor antagonist luzindole effectively blocked the effect of melatonin on locomotion, while MT2-specific antagonist 4-phenyl-2-propionamidotetralin (4-P-PDOT) and MT3-selective antagonist prazosin had no effect. Alternatively, long-term treatment with prazosin specifically altered homeostatic states of the worm, suggesting another melatonin-signaling pathway through MT3-like receptors. We also found that two G-protein alpha subunit mutants and newly isolated five mutants exhibited defects in response to melatonin. Our findings imply that melatonin acts as a neuromodulator by regulating locomotion behavior and as a ligand for homeostatic control through distinct receptor pathways in C. elegans.
Tanaka
Daisuke
D
Neuroscience Research Institute, AIST, Tsukuba, Ibaraki 305-8566, Japan.
Furusawa
Kiyotaka
K
Kameyama
Kimihiko
K
Okamoto
Harumasa
H
Doi
Motomichi
M
D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal / Q000187:drug effects; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D002845:Chromatography / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects* / Q000502:physiology; D008124:Locomotion / Q000187:drug effects* / Q000235:genetics; D008550:Melatonin / Q000378:metabolism / Q000494:pharmacology*; D044094:Receptors, Melatonin / Q000819:agonists / Q000145:classification / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013997:Time Factors
C114459:4-phenyl-2-propionamidotetraline; D029742:Caenorhabditis elegans Proteins; D044094:Receptors, Melatonin; D013764:Tetrahydronaphthalenes; D008550:Melatonin