Schwarz Nele, Hardcastle Alison J, Cheetham Michael E
UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
Vision Res. 2012 Dec 15;75:2-4. doi: 10.1016/j.visres.2012.07.016. Epub 2012 Aug 2.
The traffic of proteins to the outer segment of photoreceptors is a fundamentally important process, which when perturbed results in photoreceptor cell death. Recent reports have revealed a novel pathway for the traffic of lipid-modified proteins involving the small GTPase Arl3 and its effectors PDEδ and Unc119. The retinitis pigmentosa protein RP2 is a GTPase activating protein (GAP) for Arl3 and also appears to regulate the assembly and traffic of membrane associated protein complexes. We recently identified the Gβ subunit of transducin (Gβ1) as a novel RP2 interacting protein. Our data support a role for RP2 in facilitating membrane association and traffic of Gβ1, potentially prior to the formation of the obligate Gβ:Gγ heterodimer. Here, we review the recent evidence that suggests that RP2 co-operates with Arl3 and its effectors in protein complex assembly and membrane specification for lipid-modified proteins. This is exemplified by the co-ordination of cilia associated traffic for heterotrimeric G proteins and we propose a model for the role of Arl3 and RP2 in this process.
蛋白质运输到光感受器外段是一个极其重要的过程,一旦受到干扰,就会导致光感受器细胞死亡。最近的报告揭示了一条涉及小GTP酶Arl3及其效应物PDEδ和Unc119的脂类修饰蛋白运输新途径。视网膜色素变性蛋白RP2是Arl3的GTP酶激活蛋白(GAP),似乎也调节膜相关蛋白复合物的组装和运输。我们最近鉴定出转导素的Gβ亚基(Gβ1)是一种新的与RP2相互作用的蛋白。我们的数据支持RP2在促进Gβ1的膜结合和运输中发挥作用,这可能发生在 obligate Gβ:Gγ异二聚体形成之前。在这里,我们综述了最近的证据,这些证据表明RP2在蛋白质复合物组装和脂类修饰蛋白的膜特异性方面与Arl3及其效应物合作。异源三聚体G蛋白的纤毛相关运输协调就是一个例子,我们提出了一个Arl3和RP2在此过程中作用的模型。