Vicente-Agullo F, Rovira J C, Sala S, Sala F, Rodriguez-Ferrer C, Campos-Caro A, Criado M, Ballesta J J
Instituto de Neurociencias, Centro Mixto CSIC-Universidad Miguel Hernández, Campus de San Juan, Apartado Correos 18, 03550 San Juan de Alicante, Spain.
Biochemistry. 2001 Jul 27;40(28):8300-6. doi: 10.1021/bi010087g.
We have examined the role of a highly conserved arginine (R209), which flanks the M1 transmembrane segment of nAChRs, in the biogenesis and function of neuronal nAChRs. Point mutations revealed that, in alphaBgtx-sensitive neuronal alpha7 nAChRs, the conserved arginine is required for the transport of assembled receptors to the cell surface. By contrast, R209 does not play any role in the transport of assembled alpha-Bgtx-insensitive neuronal alpha3beta4 nAChRs to the cell surface. However, a basic residue at this position of alpha3 and beta4 subunits is necessary for either synthesis, folding, or assembly of alpha3beta4 receptors. Moreover, electrophysiological experiments revealed that in alpha3beta4 receptors the conserved arginine of the alpha3 subunit is involved in either coupling agonist binding to the channel or regulating single channel kinetics.
我们研究了一个高度保守的精氨酸（R209）在神经元烟碱型乙酰胆碱受体（nAChRs）生物合成和功能中的作用，该精氨酸位于nAChRs的M1跨膜片段两侧。点突变表明，在对α-银环蛇毒素（αBgtx）敏感的神经元α7 nAChRs中，保守的精氨酸是组装好的受体转运到细胞表面所必需的。相比之下，R209在组装好的对αBgtx不敏感的神经元α3β4 nAChRs转运到细胞表面的过程中不起任何作用。然而，α3和β4亚基这个位置的一个碱性残基对于α3β4受体的合成、折叠或组装是必需的。此外，电生理实验表明，在α3β4受体中，α3亚基保守的精氨酸要么参与将激动剂结合与通道偶联，要么参与调节单通道动力学。
