Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Neurology, Stanford University, Palo Alto, CA, USA.
Channels (Austin). 2020 Dec;14(1):110-122. doi: 10.1080/19336950.2020.1740501.
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are expressed throughout the mammalian central nervous system (CNS). These channels have been implicated in a wide range of diseases, including Major Depressive Disorder and multiple subtypes of epilepsy. The diversity of functions that HCN channels perform is in part attributable to differences in their subcellular localization. To facilitate a broad range of subcellular distributions, HCN channels are bound by auxiliary subunits that regulate surface trafficking and channel function. One of the best studied auxiliary subunits is tetratricopeptide-repeat containing, Rab8b-interacting protein (TRIP8b). TRIP8b is an extensively alternatively spliced protein whose only known function is to regulate HCN channels. TRIP8b binds to HCN pore-forming subunits at multiple interaction sites that differentially regulate HCN channel function and subcellular distribution. In this review, we summarize what is currently known about the structure and function of TRIP8b isoforms with an emphasis on the role of this auxiliary subunit in health and disease.
超极化激活环核苷酸门控 (HCN) 通道在哺乳动物中枢神经系统 (CNS) 中广泛表达。这些通道与多种疾病有关，包括重度抑郁症和多种类型的癫痫。HCN 通道执行的功能多样性部分归因于它们亚细胞定位的差异。为了促进广泛的亚细胞分布，HCN 通道被辅助亚基结合，这些辅助亚基调节表面运输和通道功能。研究最多的辅助亚基之一是四肽重复包含、Rab8b 相互作用蛋白 (TRIP8b)。TRIP8b 是一种广泛存在的选择性剪接蛋白，其唯一已知的功能是调节 HCN 通道。TRIP8b 在多个相互作用位点与 HCN 孔形成亚基结合，这些位点差异调节 HCN 通道功能和亚细胞分布。在这篇综述中，我们总结了目前关于 TRIP8b 异构体的结构和功能的知识，重点介绍了该辅助亚基在健康和疾病中的作用。
