Replacing the rod with the cone transducin α subunit decreases sensitivity and accelerates response decay
Replacing the rod with the cone transducin α subunit decreases sensitivity and accelerates response decay
复制标题
DOI：
10.1113/jphysiol.2010.191221
复制
发表时间：
2010-09-01
影响因子：
5.5
通讯作者：
Fain, G. L.
中科院分区：
文献类型：
--
作者：
Chen, C. -K.;Woodruff, M. L.;Fain, G. L.
视锥视觉不如视杆视觉灵敏。这种差异在很大程度上可以归因于感光器本身，但视锥细胞敏感度较低的原因仍不清楚。最近的记录表明，一个重要的因素可能是视锥信号转导的激活速度的差异；即每个漂白的视紫红质分子(Rh*)的视锥反应的上升阶段比每个Rh*的杆状反应的上升阶段的斜率更小，这可能是因为Rh*和磷酸二酯酶6(PDE6)效应分子的激活之间的某个步骤以较小的增益发生。由于视杆细胞和视锥细胞具有不同的G蛋白α亚基，并且该亚单位(Tα)在G蛋白与Rh*的相互作用和PDE6的激活中都起着关键作用，我们通过在视杆细胞Tα基因敲除的视杆细胞中表达视锥Tα来研究扩增差异的机制，从而产生所谓的GNA2C小鼠。我们发现，GNA2C小鼠的视杆敏感性降低，激活率是野生型(WT)小鼠视杆的一半。此外，GNA2C反应比WT反应恢复得更快，其动力学参数类似于本地小鼠的锥体。我们的结果首次表明，视杆细胞和视锥细胞在敏感性和反应动力学方面的部分差异可能是由于G蛋白α亚单位的差异所致。它们还表明，G-蛋白α的分子性质可能在整个体内G-蛋白亲代谢受体的级联动力学中发挥重要作用。
Cone vision is less sensitive than rod vision. Much of this difference can be attributed to the photoreceptors themselves, but the reason why the cones are less sensitive is still unknown. Recent recordings indicate that one important factor may be a difference in the rate of activation of cone transduction; that is, the rising phase of the cone response per bleached rhodopsin molecule (Rh*) has a smaller slope than the rising phase of the rod response per Rh*, perhaps because some step between Rh* and activation of the phosphodiesterase 6 (PDE6) effector molecule occurs with less gain. Since rods and cones have different G-protein alpha subunits, and since this subunit (T alpha) plays a key role both in the interaction of G-protein with Rh* and the activation of PDE6, we investigated the mechanism of the amplification difference by expressing cone T alpha in rod T alpha-knockout rods to produce so-called GNAT2C mice. We show that rods in GNAT2C mice have decreased sensitivity and a rate of activation half that of wild-type (WT) mouse rods. Furthermore, GNAT2C responses recover more rapidly than WT responses with kinetic parameters resembling those of native mouse cones. Our results show for the first time that part of the difference in sensitivity and response kinetics between rods and cones may be the result of a difference in the G-protein alpha subunit. They also indicate more generally that the molecular nature of G-protein alpha may play an important role in the kinetics of G-protein cascades for metabotropic receptors throughout the body.