Department of Natural and Life Sciences, The Open University of Israel, Ra'anana, Israel.
Department of Natural and Life Sciences, The Open University of Israel, Ra'anana, Israel.
J Biol Chem. 2022 Jun;298(6):101978. doi: 10.1016/j.jbc.2022.101978. Epub 2022 Apr 22.
G protein-coupled receptors are known to play a key role in many cellular signal transduction processes, including those mediating serotonergic signaling in the nervous system. Several factors have been shown to regulate the activity of these receptors, including membrane potential and the concentration of sodium ions. Whether voltage and sodium regulate the activity of serotonergic receptors is unknown. Here, we used Xenopus oocytes as an expression system to examine the effects of voltage and of sodium ions on the potency of one subtype of serotonin (5-hydroxytryptamine [5-HT]) receptor, the 5-HT receptor. We found that the potency of 5-HT in activating the receptor is voltage dependent and that it is higher at resting potential than under depolarized conditions. Furthermore, we found that removal of extracellular Na resulted in a decrease of 5-HT potency toward the 5-HT receptor and that a conserved aspartate in transmembrane domain 2 is crucial for this effect. Our results suggest that this allosteric effect of Na does not underlie the voltage dependence of this receptor. We propose that the characterization of modulatory factors that regulate this receptor may contribute to our future understanding of various physiological functions mediated by serotonergic transmission.
G 蛋白偶联受体在许多细胞信号转导过程中发挥着关键作用，包括在神经系统中介导血清素信号的过程。已经有几种因素被证明可以调节这些受体的活性，包括膜电位和钠离子浓度。电压和钠离子是否调节血清素受体的活性尚不清楚。在这里，我们使用非洲爪蟾卵母细胞作为表达系统，研究了电压和钠离子对一种血清素（5-羟色胺[5-HT]）受体亚型，即 5-HT 受体的活性的影响。我们发现 5-HT 激活受体的效力与电压有关，在静息电位下比去极化条件下更高。此外，我们发现去除细胞外 Na 会导致 5-HT 对 5-HT 受体的效力降低，并且跨膜域 2 中的一个保守天冬氨酸对这种效应至关重要。我们的结果表明，Na 的这种变构效应不是该受体电压依赖性的基础。我们提出，对调节这种受体的调节因子的特性进行表征可能有助于我们未来对各种由血清素传递介导的生理功能的理解。
