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| 鱼类神经激肽B生理功能及其分子机制 |
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王滨,田振方,郭慧英,徐永江,崔爱君,姜燕
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1.海水养殖生物育种与可持续产出全国重点实验室 中国水产科学研究院黄海水产研究所 山东 青岛 266071;2.青岛海洋科技中心海洋渔业科学与食物产出过程功能实验室 山东 青岛 266237;3.中国海洋大学水产学院 山东 青岛 266003
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| 摘要: |
| 神经激肽B (Neurokinin B, NKB)是由tac3基因编码的一种下丘脑神经肽，属于Tachykinin家族重要成员之一，主要在脑中高表达，但也表达于外周组织中，通过其受体NK3R介导参与了哺乳动物多种生理功能。目前，已在斑马鱼(Danio rerio)、草鱼(Ctenopharyngodon idellus)、尼罗罗非鱼(Oreochromis niloticus)等硬骨鱼中鉴定出NKB系统，并且NKB能够参与调节鱼类生殖和摄食等重要生理活动。本文对既有硬骨鱼NKB系统研究进行简要总结，从NKB及其受体基因鉴定、组织分布、生理功能、信号转导机制等方面进行全面概括讨论，以增加对鱼类NKB系统的认识和了解，以期为后续研究提供参考。 |
| 关键词: 鱼类 神经激肽B 组织分布 生殖 信号转导 |
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| 基金项目:国家重点研发计划(2022YFD2400401)、国家自然科学基金(32072949)、中国水产科学研究院黄海水产研究所基本科研业务费(20603022022018)、中国水产科学研究院基本科研业务费(2023TD51)和财政部和农业农村部：国家海水鱼产业技术体系(CARS-47)共同资助。 |
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| Physiological functions and molecular mechanisms of neurokinin B in fish |
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WANG Bin1,2, TIAN Zhenfang1,2, GUO Huiying1,3, XU Yongjiang1,2, CUI Aijun4,5, JIANG Yan6,7
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1.State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute,
Chinese Academy of Fishery Sciences, Qingdao 266071, China;2.Laboratory for Marine Fisheries
Science and Food Production Processes, Qingdao Marine Science and Technology Center, Qingdao 266237, China;3.Fisheries College, Ocean University of China, Qingdao 266003, China;4.State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute,
Chinese Academy of Fishery Sciences, Qingdao 266072, China;5.Laboratory for Marine Fisheries
Science and Food Production Processes, Qingdao M 攈䄥 �ᴪ 攠䄥 �ᴪ 擀䄥 �ᴪ 擠䄥 �ᴪ 摨䄥 �ᴪ 撈䄥 �ᴪ;6.State Key Laboratory of Mariculture Biobreeding and Sustainable Goods, Yellow Sea Fisheries Research Institute,
Chinese Academy of Fishery Sciences, Qingdao 266073, China;7.Laboratory for Marine Fisheries
Science and Food Production Processes, Qingdao M ￭ Ɛ 䀀܀Times New Roman 㚯䨰ᴉ 㞯Ȁ퓹Ȁ퓹
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| Abstract: |
| Neurokinin B (NKB) is a hypothalamic neuropeptide containing 10 amino acids and is an essential member of the tachykinin family. Based on studies in mammals, Kiss, NKB, and dynorphin A are located in the common neurons, named KNDy neurons, and NKB and Kiss can stimulate the GnRH pulses. In humans, the mutations of NKB and its receptor NK3R can lead to hypogonadotropic hypogonadism and infertility. NKB is also involved in many other physiological activities in mammals and has received increasing attention. NKB was first purified from porcine spinal cord extracts and named neurokinin B or neuromedin K. Subsequently, NKB has been identified in various species, and its encoding gene was named tac2 in ruminants and rodents, and tac3 in other mammals, birds, reptiles, amphibians, and fish. In teleosts, the NKB system was first identified in zebrafish by three laboratories in 2012; it was also found in grass carp, goldfish, Nile tilapia, European eel, orange-spotted grouper, and half-smooth tongue.
As teleosts have experienced the third round of genome duplication (3R), the bony fish have two forms of tac3 genes, namely tac3a and tac3b. However, only tac3a is present in highly evolved fish species, such as Nile tilapia and orange-spotted grouper, whereas the tac3b gene has been lost. tac3 in fish and amphibians can encode two mature peptides, NKB and an NKB-related peptide (NKBRP), whereas there is only NKB in mammals, birds, and reptiles. NKB and NKBRP sequences are highly conserved, and sequence analysis showed that NKB and NKBRP share an identical -FXGLM motif at the C-terminus, and X is a hydrophobic or aromatic amino acid residue, which plays an important role in binding to homologous receptors.
NKB exerts biological effects by activating the endogenous receptor NK3R. The NK3R receptor belongs to the G protein-coupled receptor family and has a typical seven-transmembrane structure. NK3R is encoded by the tacr3 gene. There are two tacr3 subtypes in teleosts: tacr3a and tacr3b. There was an additional gene, called tacr3a2, in the zebrafish and grass carp, and it was produced by local genome duplication of tacr3a1. The tissue distribution shows that tac3 and tacr3 are widely expressed in the central nervous system and peripheral tissues, indicating that they have essential physiological functions. The specific expression patterns vary depending on the species. They are mainly expressed in the brain, with high expression levels in the pituitary, intestine, and gonads. NKB may participate in regulating reproduction and feeding in teleosts.
Currently, studies in teleosts mainly focus on reproductive and feeding regulation. Due to the existence of multiple forms of tac3 and tacr3 genes in teleosts, the action of the NKB system on reproduction control is more complex. Using different experiment methods, such as intraperitoneal injection, intramuscular injection, and incubation of pituitary cells or pituitaries, NKB affected the expression of gnrh, kiss, lhβ, and fshβ and the secretion of LH, FSH, and E2 in fish. The physiological effects varied depending on the gonadal development stages, species, sex, treatment methods, treatment time, and dose. In addition, NKB can act as an anorectic peptide to inhibit food intake and promote gastrointestinal motility. It could also affect the expression of growth-related genes. In summary, as a neurotransmitter or neuromodulator in the central nervous system and a major member of the brain-gut peptides, the NKB system plays an important role in teleosts.
Tachykinins activate receptors by coupling to Gαs and Gαq proteins, transducing its signals via PKA and PKC pathways. NKB and NKBRP could activate the PKA/PKC pathway via cognate receptors in some teleosts. This could be verified because different pathway inhibitors could block the effects of NKB and NKBRP. Upon binding to NK3R, NKB induces the secretion of related neuropeptides and the expression of related genes through the AC/cAMP/PKA, PLC/IP3/PKC, and Ca2+/CaM/CaMK-II cascades. The C-terminal motif of NKB is crucial to binding receptors; once it is changed, NKB cannot activate the downstream signaling of NK3R, indicating that the integrity of the NKB/NK3R system is essential for the normal functioning of NKB. There are many deficiencies in the research regarding the function of NKB in teleosts. The specific effects and mechanisms of regulating reproductive endocrinology remain unclear, and the functional and signaling interactions between NKB and other neuroendocrine factors such as Kiss, GnIH, and GnRH require further study. In addition, the physiological functions of NKB in fish are mainly focused on reproductive regulation, with less attention given to feeding regulation and other physiological effects.
In conclusion, this review provides a summary of the research progress on the NKB system in teleosts, including the identification, tissue distribution, physiological functions, and signaling mechanisms of NKB and its receptors, to enhance the understanding of the NKB system in fish and provide a reference for future research. |
| Key words: Fish Neurokinin B Tissue distribution Reproduction Signal transduction |
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