Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Cell Mol Neurobiol. 2012 Aug;32(6):907-18. doi: 10.1007/s10571-012-9830-6. Epub 2012 Mar 27.
Rhes, the Ras Homolog Enriched in Striatum, is a GTP-binding protein whose gene was discovered during a screen for mRNAs preferentially expressed in rodent striatum. This 266 amino acid protein is intermediate in size between small Ras-like GTP-binding proteins and α-subunits of heterotrimeric G proteins. It is most closely related to another Ras-like GTP-binding protein termed Dexras1 or AGS1. Although subsequent studies have shown that the rhes gene is expressed in other brain areas in addition to striatum, the striatal expression level is relatively high, and Rhes protein is likely to play a vital role in striatal physiology and pathology. Indeed, it has recently been shown to interact with the Huntingtin protein and play a pivotal role in the selective vulnerability of striatum in Huntington's disease (HD). Not surprisingly, Rhes can interact with multiple proteins to affect striatal physiology at multiple levels. Functional studies have indicated that Rhes plays a role in signaling by striatal G protein-coupled receptors (GPCR), although the details of the mechanism remain to be determined. Rhes has been shown to bind to both α- and β-subunits of heterotrimeric G proteins and to affect signaling by both Gi/o- and Gs/olf-coupled receptors. In this context, Rhes can be classified as a member of the family of accessory proteins to GPCR signaling. With documented effects in dopamine- and opioid-mediated behaviors, an interaction with thyroid hormone systems and a role in HD pathology, Rhes is emerging as an important protein in striatal physiology and pathology.
Rhes，富含纹状体的 Ras 同源物，是一种 GTP 结合蛋白，其基因是在筛选优先在啮齿动物纹状体中表达的 mRNA 时发现的。这种 266 个氨基酸的蛋白质在大小上介于小 Ras 样 GTP 结合蛋白和异源三聚体 G 蛋白的α亚基之间。它与另一种称为 Dexras1 或 AGS1 的 Ras 样 GTP 结合蛋白最为密切相关。尽管随后的研究表明 rhes 基因除了纹状体之外还在其他脑区表达，但纹状体的表达水平相对较高，Rhes 蛋白很可能在纹状体的生理学和病理学中发挥重要作用。事实上，最近已经表明它与 Huntingtin 蛋白相互作用，并在亨廷顿病（HD）中纹状体的选择性易损性中发挥关键作用。毫不奇怪，Rhes 可以与多种蛋白质相互作用，在多个水平上影响纹状体的生理学。功能研究表明，Rhes 在纹状体 G 蛋白偶联受体（GPCR）的信号转导中发挥作用，尽管其机制的细节仍有待确定。已经表明 Rhes 与异源三聚体 G 蛋白的α和β亚基结合，并影响 Gi/o 和 Gs/olf 偶联受体的信号转导。在这种情况下，Rhes 可以归类为 GPCR 信号转导辅助蛋白家族的成员。由于在多巴胺和阿片介导的行为中具有已记录的作用，与甲状腺激素系统相互作用以及在 HD 病理学中的作用，Rhes 正在成为纹状体生理学和病理学中的重要蛋白。
