Subunit dissociation and diffusion determine the subcellular localization of rod and cone transducins
Subunit dissociation and diffusion determine the subcellular localization of rod and cone transducins
复制标题
DOI：
10.1523/jneurosci.1421-07.2007
复制
发表时间：
2007-05-16
影响因子：
5.3
通讯作者：
Slepak, Vladlen Z.
中科院分区：
文献类型：
--
作者：
Rosenzweig, Derek H.;Nair, K. Saidas;Slepak, Vladlen Z.
视杆细胞光感受器的激活诱导异源三聚体G蛋白转导素的大量重新分布。在黑暗中，转导蛋白被隔离在视杆细胞的富含膜的外节内。在光中，它分散在整个神经元中。我们在这里表明，重新分配杆transducin光需要激活，但它不需要ATP。这一观察排除了分子马达参与再分配过程的可能性。与视杆细胞中视杆细胞转导蛋白的光刺激重新分布相反，视锥细胞中视锥细胞转导蛋白在激活过程中不会重新分布。值得注意的是，当视锥细胞转导蛋白在视杆细胞中表达时，它确实经历了光刺激的再分布。我们在这里表明，激活杆和锥G-蛋白的亚细胞定位的差异与它们对膜的亲和力相关。激活的视杆细胞转导蛋白从细胞膜释放，而激活的视锥细胞转导蛋白保持与细胞膜结合。一种合成肽，解离G-蛋白复合物独立于激活促进分散的杆和锥转导细胞内。该肽还促进两种G蛋白从膜上脱离。总之，这些结果表明，它是转导蛋白的解离状态，决定其在光感受器的定位。当视杆细胞转导蛋白受到刺激时，它的亚基解离，离开外节膜，并在整个细胞中平衡。视锥细胞转导素亚基在激活过程中不解离，并保持隔离在外节内。这些发现表明，一些异源三聚体G蛋白的亚基在其天然环境中活化期间保持相关。
Activation of rod photoreceptors by light induces a massive redistribution of the heterotrimeric G-protein transducin. In darkness, transducin is sequestered within the membrane-enriched outer segments of the rod cell. In light, it disperses throughout the entire neuron. We show here that redistribution of rod transducin by light requires activation, but it does not require ATP. This observation rules out participation of molecular motors in the redistribution process. In contrast to the light-stimulated redistribution of rod transducin in rods, cone transducin in cones does not redistribute during activation. Remarkably, when cone transducin is expressed in rods, it does undergo light-stimulated redistribution. We show here that the difference in subcellular localization of activated rod and cone G-proteins correlates with their affinity for membranes. Activated rod transducin releases from membranes, whereas activated cone transducin remains bound to membranes. A synthetic peptide that dissociates G-protein complexes independently of activation facilitates dispersion of both rod and cone transducins within the cells. This peptide also facilitates detachment of both G-proteins from the membranes. Together, these results show that it is the dissociation state of transducin that determines its localization in photoreceptors. When rod transducin is stimulated, its subunits dissociate, leave outer segment membranes, and equilibrate throughout the cell. Cone transducin subunits do not dissociate during activation and remain sequestered within the outer segment. These findings indicate that the subunits of some heterotrimeric G-proteins remain associated during activation in their native environments.