Huang Weiling, Zhong Xingxing, Zampronio Cleidiane G, Bottrill Andrew R, Jones Kite G E, Tinoco Ana B, Guo Lijin, Egertová Michaela, Mirabeau Olivier, Elphick Maurice R
Centre for Evolutionary and Functional Genomics, School of Biological and Behavioural Sciences, Queen Mary University of London, London E1 4NS, United Kingdom.
Proteomics Facility Research Technology Platform, School of Life Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom.
Proc Natl Acad Sci U S A. 2025 Apr;122(13):e2420966122. doi: 10.1073/pnas.2420966122. Epub 2025 Mar 28.
Neuropeptide signaling systems are key regulators of physiological and behavioral processes in animals. However, the evolutionary history of some neuropeptides originally discovered in vertebrates is unknown. The peptide bombesin (BN) was first isolated from the skin of the toad and subsequently BN-related neuropeptides have been identified in other chordates, including gastrin-releasing peptide (GRP) and neuromedin B (NMB) in mammals, and a GRP-like peptide in the cephalochordate . However, BN-type neuropeptides have hitherto not been identified in any nonchordate animals. Here, we report the discovery and functional characterization of a BN-type neuropeptide signaling system in an echinoderm-the starfish . BN-type precursor proteins were identified in several echinoderm species based on their amino acid sequences and gene structures, and the mature structure of the BN-type neuropeptide ArBN was determined using mass spectrometry. A protein related to vertebrate GRP/NMB-type G protein-coupled receptors was identified experimentally as the receptor for ArBN in . Analysis of the distribution of the ArBN precursor in using mRNA in situ hybridization and immunohistochemistry revealed a widespread pattern of expression in the central nervous system, digestive system, and locomotory organs. Moreover, effects of ArBN in included contraction and retraction of the evertible stomach and inhibition of feeding behavior. Our findings show that the evolutionary history of BN-type neuropeptide signaling can be traced back to the deuterostome common ancestor of echinoderms and chordates. Furthermore, an ancient role of BN-type neuropeptides as regulators of feeding behavior has been revealed.
神经肽信号系统是动物生理和行为过程的关键调节因子。然而，一些最初在脊椎动物中发现的神经肽的进化史尚不清楚。蛙皮素（BN）最初是从蟾蜍皮肤中分离出来的，随后在其他脊索动物中也发现了与BN相关的神经肽，包括哺乳动物中的胃泌素释放肽（GRP）和神经介素B（NMB），以及头索动物中的一种GRP样肽。然而，迄今为止，在任何非脊索动物中都未发现BN型神经肽。在此，我们报告了在一种棘皮动物——海星中发现的BN型神经肽信号系统及其功能特征。基于氨基酸序列和基因结构，在几种棘皮动物物种中鉴定出了BN型前体蛋白，并使用质谱法确定了BN型神经肽ArBN的成熟结构。通过实验鉴定出一种与脊椎动物GRP/NMB型G蛋白偶联受体相关的蛋白作为海星中ArBN的受体。利用mRNA原位杂交和免疫组织化学分析ArBN前体在海星中的分布，结果显示其在中枢神经系统、消化系统和运动器官中广泛表达。此外，ArBN对海星的作用包括可外翻胃的收缩和回缩以及对摄食行为的抑制。我们的研究结果表明，BN型神经肽信号的进化史可以追溯到棘皮动物和脊索动物的后口动物共同祖先。此外，还揭示了BN型神经肽作为摄食行为调节因子的古老作用。
