Department of Chemistry, Brigham Young University, Provo, Utah 84602, USA.
J Neurosci. 2013 May 1;33(18):7941-51. doi: 10.1523/JNEUROSCI.5001-12.2013.
G-protein β subunits perform essential neuronal functions as part of G-protein βγ and Gβ5-regulators of G-protein signaling (RGS) complexes. Both Gβγ and Gβ5-RGS are obligate dimers that are thought to require the assistance of the cytosolic chaperonin CCT and a cochaperone, phosducin-like protein 1 (PhLP1) for dimer formation. To test this hypothesis in vivo, we deleted the Phlp1 gene in mouse (Mus musculus) retinal rod photoreceptor cells and measured the effects on G-protein biogenesis and visual signal transduction. In the PhLP1-depleted rods, Gβγ dimer formation was decreased 50-fold, resulting in a >10-fold decrease in light sensitivity. Moreover, a 20-fold reduction in Gβ5 and RGS9-1 expression was also observed, causing a 15-fold delay in the shutoff of light responses. These findings conclusively demonstrate in vivo that PhLP1 is required for the folding and assembly of both Gβγ and Gβ5-RGS9.
G 蛋白β亚基作为 G 蛋白βγ和 Gβ5-调节 G 蛋白信号（RGS）复合物的一部分，发挥着重要的神经元功能。Gβγ 和 Gβ5-RGS 都是必需的二聚体，被认为需要细胞质伴侣蛋白 CCT 和共伴侣 PhLP1 的协助才能形成二聚体。为了在体内验证这一假设，我们在小鼠（Mus musculus）视网膜杆状光感受器细胞中敲除了 Phlp1 基因，并测量了其对 G 蛋白生物发生和视觉信号转导的影响。在 PhLP1 耗尽的杆状细胞中，Gβγ 二聚体的形成减少了 50 倍，导致光敏感性降低了 10 倍以上。此外，还观察到 Gβ5 和 RGS9-1 的表达减少了 20 倍，导致光反应的关闭延迟了 15 倍。这些发现确凿地证明了 PhLP1 在体内是 Gβγ 和 Gβ5-RGS9 的折叠和组装所必需的。
