van Hooft J A, Spier A D, Yakel J L, Lummis S C, Vijverberg H P
Research Institute of Toxicology, Utrecht University, P.O. Box 80. 176, NL-3508 TD Utrecht, The Netherlands.
Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11456-61. doi: 10.1073/pnas.95.19.11456.
Serotonin (5-hydroxytryptamine) type 3 receptors (5-HT3R) and nicotinic acetylcholine receptors are structurally and functionally related proteins, yet distinct members of the family of ligand-gated ion channels. For most members of this family a diversity of heteromeric receptors is known at present. In contrast, known 5-HT3R subunits are all homologs of the same 5-HT3R-A subunit and form homopentameric receptors. Here we show, by heterologous expression followed by immunoprecipitation, that 5-HT3R and nicotinic acetylcholine receptor alpha4 subunits coassemble into a novel type of heteromeric ligand-gated ion channel, which is activated by 5-HT. The Ca2+ permeability of this heteromeric ion channel is enhanced as compared with that of the homomeric 5-HT3R channel. Heteromeric 5-HT3/alpha4 and homomeric 5-HT3Rs have similar pharmacological profiles, but distinct sensitivities to block by the antagonist d-tubocurarine. Coassembly of subunits beyond the boundaries of ligand-gated ion channel families may constitute an important mechanism contributing to the diverse properties and functions of native neurotransmitter receptors.
5-羟色胺（5-羟色胺）3型受体（5-HT3R）和烟碱型乙酰胆碱受体在结构和功能上是相关蛋白，但属于配体门控离子通道家族的不同成员。目前已知该家族的大多数成员存在多种异聚体受体。相比之下，已知的5-HT3R亚基都是同一5-HT3R-A亚基的同源物，并形成同五聚体受体。在这里，我们通过异源表达后进行免疫沉淀表明，5-HT3R和烟碱型乙酰胆碱受体α4亚基共同组装成一种新型的异聚体配体门控离子通道，该通道可被5-羟色胺激活。与同聚体5-HT3R通道相比，这种异聚体离子通道的Ca2+通透性增强。异聚体5-HT3/α4和同聚体5-HT3R具有相似的药理学特征，但对拮抗剂d-筒箭毒碱阻断的敏感性不同。配体门控离子通道家族界限之外的亚基共同组装可能是一种重要机制，有助于天然神经递质受体具有多样的特性和功能。
