Department of Ophthalmology, John A. Moran Eye Center, University of Utah Health Science Center, 65 Mario Capecchi Drive, 84132, Salt Lake City, UT, USA,
Adv Exp Med Biol. 2014;801:487-93. doi: 10.1007/978-1-4614-3209-8_62.
PrBP/δ, encoded by the Pde6d gene, is an isoprenyl-binding protein that regulates trafficking of isoprenylated proteins, such as PDE6 and GRK1, from photoreceptor inner segments to outer segments. Trafficking of PDE6 and GRK1 to photoreceptor outer segments is impeded in Pde6d knockout mice. In Pde6d (-/-) cones, PDE6 and GRK1 are nearly undetectable and the b-wave amplitudes of photopic ERGs in Pde6d (-/-) mice are reduced by over 50 %. We reported recently that UNC119, a homolog of PrBP/δ highly expressed in photoreceptors, functions as an acyl-binding protein and regulates transport of G-proteins in sensory neurons. Since both PrBP/δ and UNC119 regulate peripheral protein trafficking in photoreceptors, we generated Pde6d; Unc119 double knockout mice in order to study how PrBP/δ and UNC119 may interact. Surprisingly, knockout of Unc119 partially reversed the transport defect of GRK1 in cone photoreceptors caused by deletion of Pde6d, and the b-wave amplitudes of photopic ERGs in the double knockout mice were significantly higher than those in the Pde6d (-/-) mice. These results suggest that cone transport of isoprenylated and acylated proteins is interdependent.
PrBP/δ 由 Pde6d 基因编码，是一种异戊烯基结合蛋白，可调节异戊烯化蛋白（如 PDE6 和 GRK1）从光感受器内节到外节的运输。Pde6d 敲除小鼠中 PDE6 和 GRK1 的运输受到阻碍。在 Pde6d (-/-) 锥体中，PDE6 和 GRK1 几乎无法检测到，并且 Pde6d (-/-) 小鼠中的光诱发 ERG 的 b 波幅度降低超过 50%。我们最近报道 UNC119，一种在光感受器中高度表达的 PrBP/δ 同源物，作为酰基结合蛋白发挥作用，调节感觉神经元中 G 蛋白的运输。由于 PrBP/δ 和 UNC119 均可调节光感受器中周围蛋白的运输，因此我们生成了 Pde6d;Unc119 双敲除小鼠，以研究 PrBP/δ 和 UNC119 可能如何相互作用。令人惊讶的是，UNC119 的敲除部分逆转了 Pde6d 缺失引起的 GRK1 在锥体光感受器中的运输缺陷，并且双敲除小鼠的光诱发 ERG 的 b 波幅度明显高于 Pde6d (-/-) 小鼠。这些结果表明异戊烯化和酰化蛋白的锥体运输是相互依赖的。
