Department of Physiology, Seoul National University, College of Medicine, Biomedical Science Building 117, 103 Daehakro, Jongro-gu, Seoul, 110-799, South Korea.
Department of Physiology, University of California, San Francisco, CA, 94158-2517, USA.
Pflugers Arch. 2018 Mar;470(3):505-516. doi: 10.1007/s00424-017-2095-7. Epub 2017 Dec 11.
Polycystic kidney disease 2-like-1 (PKD2L1), or polycystin-L or TRPP2, formerly TRPP3, is a transient receptor potential (TRP) superfamily member. It is a calcium-permeable non-selective cation channel that regulates intracellular calcium concentration and thereby calcium signaling. PKD2L1 has been reported to take part in hedgehog signaling in renal primary cilia and sour tasting coupling with PKD1L3. In addition to the previous reports, PKD2L1 is recently found to play a crucial role in localization with β2-adrenergic receptor (β2AR) on the neuronal primary cilia. The disruption of PKD2L1 leads to the loss of β2AR on the primary cilia and reduction in intracellular concentration of cyclic adenosine monophosphate (cAMP). Since the role of cAMP and PKA is frequently mentioned in the studies of PKD diseases, we investigated on the mechanism of cAMP regulation in relation to the function of PKD2L1 channel. In this study, we observed the activity of PKD2L1 channel increased by the downstream cascades of β2AR and found the clustered phosphorylation sites, Ser-682, Ser-685, and Ser-686 that are significant in the channel regulation by phosphorylation.
多囊肾病 2 型相关蛋白 1（PKD2L1），也称为多囊蛋白-L 或 TRPP2，以前称为 TRPP3，是瞬时受体电位（TRP）超家族成员。它是一种钙通透性非选择性阳离子通道，可调节细胞内钙离子浓度，从而调节钙信号。已有报道称 PKD2L1 参与肾脏初级纤毛中的 hedgehog 信号传导以及与 PKD1L3 的酸味耦合。除了之前的报道外，最近还发现 PKD2L1 在神经元初级纤毛上与 β2-肾上腺素能受体（β2AR）的定位中发挥关键作用。PKD2L1 的破坏导致 β2AR 在初级纤毛上丢失，细胞内环腺苷酸（cAMP）浓度降低。由于 cAMP 和 PKA 的作用在 PKD 疾病的研究中经常被提及，我们研究了与 PKD2L1 通道功能相关的 cAMP 调节机制。在这项研究中，我们观察到 PKD2L1 通道的活性被 β2AR 的下游级联增加，并发现了在磷酸化调节通道方面具有重要意义的簇状磷酸化位点 Ser-682、Ser-685 和 Ser-686。
