La Trobe Institute for Molecular Science, La Trobe University, Bendigo, Victoria, Australia.
Department of Rural Clinical Sciences, La Trobe University, Bendigo, Victoria, Australia.
PLoS One. 2023 Mar 1;18(3):e0281507. doi: 10.1371/journal.pone.0281507. eCollection 2023.
The 5-hydroxytrptamine 3 (5-HT3) receptor is a member of the 'Cys-loop' family and the only pentameric ligand gated ion channel among the serotonin receptors. 5-HT3 receptors play an important role in controlling growth, development, and behaviour in animals. Several 5-HT3 receptor antagonists are used to treat diseases (e.g., irritable bowel syndrome, nausea and emesis). Humans express five different subunits (A-E) enabling a variety of heteromeric receptors to form but all contain 5HT3A subunits. However, the information available about the 5-HT3 receptor subunit occurrence among the metazoan lineages is minimal. In the present article we searched for 5-HT3 receptor subunit homologs from different phyla in Metazoa. We identified more than 1000 5-HT3 receptor subunits in Metazoa in different phyla and undertook simultaneous phylogenetic analysis of 526 5HT3A, 358 5HT3B, 239 5HT3C, 70 5HT3D, and 173 5HT3E sequences. 5-HT3 receptor subunits were present in species belonging to 11 phyla: Annelida, Arthropoda, Chordata, Cnidaria, Echinodermata, Mollusca, Nematoda, Orthonectida, Platyhelminthes, Rotifera and Tardigrada. All subunits were most often identified in Chordata phylum which was strongly represented in searches. Using multiple sequence alignment, we investigated variations in the ligand binding region of the 5HT3A subunit protein sequences in the metazoan lineage. Several critical amino acid residues important for ligand binding (common structural features) are commonly present in species from Nematoda and Platyhelminth gut parasites through to Chordata. Collectively, this better understanding of the 5-HT3 receptor evolutionary patterns raises possibilities of future pharmacological challenges facing Metazoa including effects on parasitic and other species in ecosystems that contain 5-HT3 receptor ligands.
5-羟色胺 3（5-HT3）受体是“Cys 环”家族的成员，也是 5-羟色胺受体中唯一的五聚体配体门控离子通道。5-HT3 受体在控制动物的生长、发育和行为方面发挥着重要作用。几种 5-HT3 受体拮抗剂被用于治疗疾病（例如，肠易激综合征、恶心和呕吐）。人类表达五种不同的亚基（A-E），能够形成多种异源受体，但都包含 5-HT3A 亚基。然而，关于后生动物谱系中 5-HT3 受体亚基存在的信息非常有限。在本文中，我们从后生动物门的不同门中搜索 5-HT3 受体亚基的同源物。我们在后生动物门的不同门中鉴定出了超过 1000 个 5-HT3 受体亚基，并对 526 个 5-HT3A、358 个 5-HT3B、239 个 5-HT3C、70 个 5-HT3D 和 173 个 5-HT3E 序列进行了同时的系统发育分析。5-HT3 受体亚基存在于属于 11 个门的物种中：环节动物门、节肢动物门、脊索动物门、刺胞动物门、棘皮动物门、软体动物门、线虫门、直泳虫门、扁形动物门、轮形动物门和缓步动物门。所有亚基最常被鉴定为脊索动物门，在搜索中得到了强烈的代表。使用多重序列比对，我们研究了后生动物谱系中 5-HT3A 亚基蛋白序列的配体结合区域的变异。几个对配体结合（共同结构特征）重要的关键氨基酸残基在从线虫门和扁形动物门肠道寄生虫到脊索动物门的物种中普遍存在。总的来说，对 5-HT3 受体进化模式的更好理解提高了后生动物面临的未来药理学挑战的可能性，包括对含有 5-HT3 受体配体的生态系统中的寄生虫和其他物种的影响。
