The GPCR properties of polycystin-1- A new paradigm.
The GPCR properties of polycystin-1- A new paradigm.
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DOI：
10.3389/fmolb.2022.1035507
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发表时间：
2022
影响因子：
5
通讯作者：
中科院分区：
文献类型：
--
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多囊蛋白-1(Polycystin-1，PC1)是由常染色体显性遗传性多囊肾病(ADPKD)最常见的突变基因PKD1编码的含有11个跨膜(TM)结构域的蛋白。这个大的(>；462kDal)蛋白有一个复杂的翻译后成熟过程，已经描述了五个以上的蛋白水解性切割，并在多个细胞位置发现。20多年前首次描述了胞质C-末端尾部(C-α)膜旁区域与异源三聚体G-Tail I/o的结合和激活，开启了对PC_1的S潜在功能作为一种新的G蛋白偶联受体的研究和争议的大门。随后的生化和基于细胞的分析表明，PC1C-Tail能够结合G-α蛋白家族的许多成员，并抑制或激活参与离子通道活性调节、转录因子激活和细胞凋亡的G蛋白依赖通路。最近的工作表明，PC1介导的G蛋白调节在防止肾囊肿发展中起着重要作用；然而，PC1调节G蛋白活性的机制仍在不断被发现。PC1与7-TM GPCRs的粘附类相似，最显著的是在第一个TM结构域之前有一个保守的GPCR蛋白水解点(GPS)，它经历了自我催化的蛋白分解切割，这表明PC1介导的G蛋白信号调节的潜在机制。本文综述了支持PC1的GPCR样功能及其与囊性疾病的相关性的证据，讨论了GPS裂解和潜在的配体参与调节PC1的GPCR样功能，并探讨了PC1GPCR样活性与多囊蛋白受体-通道复合体的通道特性调节之间的潜在联系。
Polycystin-1 (PC1) is an 11-transmembrane (TM) domain-containing protein encoded by the PKD1 gene, the most frequently mutated gene leading to autosomal dominant polycystic kidney disease (ADPKD). This large (> 462 kDal) protein has a complex posttranslational maturation process, with over five proteolytic cleavages having been described, and is found at multiple cellular locations. The initial description of the binding and activation of heterotrimeric Gαi/o by the juxtamembrane region of the PC1 cytosolic C-terminal tail (C-tail) more than 20 years ago opened the door to investigations, and controversies, into PC1’s potential function as a novel G protein-coupled receptor (GPCR). Subsequent biochemical and cellular-based assays supported an ability of the PC1 C-tail to bind numerous members of the Gα protein family and to either inhibit or activate G protein-dependent pathways involved in the regulation of ion channel activity, transcription factor activation, and apoptosis. More recent work has demonstrated an essential role for PC1-mediated G protein regulation in preventing kidney cyst development; however, the mechanisms by which PC1 regulates G protein activity continue to be discovered. Similarities between PC1 and the adhesion class of 7-TM GPCRs, most notably a conserved GPCR proteolysis site (GPS) before the first TM domain, which undergoes autocatalyzed proteolytic cleavage, suggest potential mechanisms for PC1-mediated regulation of G protein signaling. This article reviews the evidence supporting GPCR-like functions of PC1 and their relevance to cystic disease, discusses the involvement of GPS cleavage and potential ligands in regulating PC1 GPCR function, and explores potential connections between PC1 GPCR-like activity and regulation of the channel properties of the polycystin receptor-channel complex.
卵果冻蛋白（SPREJ）的10个海胆受体是多囊肾脏病1（PKD1）家族的成员。
影响因子：
4.4
作者：
Gunaratne, H. Jayantha;Moy, Gary W.;Kinukawa, Masashi;Miyata, Shinji;Mah, Silvia A.;Vacquier, Victor D.
通讯作者：
Vacquier, Victor D.
影响因子：
3.7
作者：
Parnell SC;Puri S;Wallace DP;Calvet JP
通讯作者：
Calvet JP