ISSN: 1449-2288International Journal of Biological Sciences
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Int J Biol Sci 2023; 19(9):2914-2933. doi:10.7150/ijbs.81055 This issue Cite
Research Paper
Melatonin modulates the hypothalamic-pituitary neuroendocrine axis to regulate physiological color change in teleost fish
1. National Engineering Laboratory of Marine Germplasm Resources Exploration and Utilization, Marine Science College, Zhejiang Ocean University, Zhoushan, Zhejiang 316022, People's Republic of China.
2. Institute of Biochemistry, College of Life Sciences, Zijingang Campus, Zhejiang University, Hangzhou, Zhejiang 310058, People's Republic of China.
3. Programs in Human Genetics and Biological Sciences, Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, United States.
#These authors contributed equally
Abstract
Melatonin (MT) is a crucial neuroendocrine regulator of various physiological activities in vertebrates, especially in circadian or seasonal rhythm control. In the present study, the large yellow croaker (Larimichthys crocea), a marine bony fish with circadian body color change behavior, is chosen for functional investigation on teleost MT signaling systems that remain uncharacterized. All five melatonin receptors (LcMtnr1a1, LcMtnr1a2, LcMtnr1b1, LcMtnr1b2, and LcMtnr1c) were significantly activated by MT, triggering extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation through different G protein coupling signaling pathways, with exclusive Gαi-dependency for LcMtnr1a2 and LcMtnr1c, and Gαq-dependency for two LcMtnr1b paralogs, whereas LcMtnr1a1 activated Gαi and Gαs dual-dependent signaling pathways. A comprehensive model of the MT signaling system in the hypothalamic-pituitary neuroendocrine axis was further constructed based on ligand-receptor interaction analysis using single-cell RNA-seq data, as well as spatial expression patterns of Mtnrs and related neuropeptides in central neuroendocrine tissues. A novel regulatory pathway of MT/melanin-concentrating hormone (MCH) and MT/(tachykinin precursor 1 (TAC1)+corticotropin-releasing hormone (CRH))/melanocyte-stimulating hormone (MSH) was discovered that functions in chromatophore mobilization and physiological color change and was further validated by pharmacological experiments. Together, our findings define multiple intracellular signaling pathways mediated by L. crocea melatonin receptors and provide the first in-depth evidence that uncover the upstream modulating roles of the MT signaling system in the hypothalamic-pituitary neuroendocrine axis of a marine teleost species, particularly in chromatophore mobilization and physiological color change.
Keywords: melatonin receptors, cell signaling, single-cell RNA-seq, hypothalamic-pituitary axis, chromatophores
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