Department of Pharmacology, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
Cell Mol Life Sci. 2011 Sep;68(17):2951-60. doi: 10.1007/s00018-010-0603-4. Epub 2010 Dec 9.
Primary cilia are nearly ubiquitous cellular appendages that provide important sensory and signaling functions. Ciliary dysfunction underlies numerous human diseases, collectively termed ciliopathies. Primary cilia have distinct functions on different cell types and these functions are defined by the signaling proteins that localize to the ciliary membrane. Neurons throughout the mammalian brain possess primary cilia upon which certain G protein-coupled receptors localize. Yet, the precise signaling proteins present on the vast majority of neuronal cilia are unknown. Here, we report that dopamine receptor 1 (D1) localizes to cilia on mouse central neurons, thereby implicating neuronal cilia in dopamine signaling. Interestingly, ciliary localization of D1 is dynamic, and the receptor rapidly translocates to and from cilia in response to environmental cues. Notably, the translocation of D1 from cilia requires proteins mutated in the ciliopathy Bardet-Biedl syndrome (BBS), and we find that one of the BBS proteins, Bbs5, specifically interacts with D1.
纤毛是几乎普遍存在于细胞上的附属物，它们提供重要的感觉和信号功能。纤毛功能障碍是许多人类疾病的基础，这些疾病统称为纤毛病。纤毛在不同的细胞类型上具有不同的功能，这些功能是由定位于纤毛膜的信号蛋白来定义的。哺乳动物大脑中的神经元都有纤毛，某些 G 蛋白偶联受体就定位于其上。然而，绝大多数神经元纤毛上存在的确切信号蛋白尚不清楚。在这里，我们报告多巴胺受体 1（D1）定位于小鼠中枢神经元的纤毛上，从而表明神经元纤毛参与多巴胺信号转导。有趣的是，D1 在纤毛上的定位是动态的，受体可以根据环境线索快速地从纤毛中转位到纤毛，再从纤毛中转位回来。值得注意的是，D1 从纤毛中的转位需要突变的纤毛病 Bardet-Biedl 综合征（BBS）中的蛋白质，我们发现 BBS 蛋白之一 Bbs5 与 D1 特异性相互作用。
