Polycystin-1 Interacting Protein-1 (CU062) Interacts with the Ectodomain of Polycystin-1 (PC1).
Polycystin-1 Interacting Protein-1 (CU062) Interacts with the Ectodomain of Polycystin-1 (PC1).
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Polycystin-1相互作用的蛋白-1（CU062）与多囊这1（PC1）的外生域相互作用。
作者：
编码多囊蛋白-1 （PC1）的PKD1基因与85%的常染色体显性多囊肾病（ADPKD）病例有关。PC1已被证明存在于尿外泌体样囊泡（PKD - ELVs）中，并且在生殖系PKD1突变的个体中降低。对正常个体和PKD1突变个体的尿PKD - elv进行无标记质谱比较，结果显示，几种蛋白质的减少程度与PC1水平的下降相匹配。其中一些蛋白质，如多囊蛋白-2 (PC2)，可能存在于与pc1 -多囊蛋白复合物（PCC）的高阶多蛋白组装中。CU062 （Q9NYP8）在ADPKD PKD−elv中减少，因此是候选的PCC成分。CU062是一种小糖蛋白，具有信号肽，但没有跨膜结构域，可以与自身寡聚并与PC1相互作用。利用免疫荧光（IF）技术研究CU062与PC1、PC2的定位。在非融合细胞中，所有三种蛋白都定位于局灶粘连（FAs）、缩回纤维（rf）和rf相关的细胞外囊泡（migrasomes）附近。在融合细胞中，原发纤毛有PC1/PC2/CU062 +细胞外囊泡粘附在其质膜上。在暴露于线粒体解耦剂的细胞中，我们检测到新的PC1/CU062 +环状结构的发展，这些结构携带了肿胀的线粒体。在线粒体应激下接触抑制的细胞中，PC1、PC2和CU062在大的、顶端出芽的细胞外囊泡上被观察到，其中蛋白质在膜上形成网状网络。CU062与PC1相互作用，可能在识别衰老线粒体及其在细胞外囊泡中的挤压中发挥作用。
The PKD1 gene, encoding protein polycystin-1 (PC1), is responsible for 85% of cases of autosomal dominant polycystic kidney disease (ADPKD). PC1 has been shown to be present in urinary exosome−like vesicles (PKD−ELVs) and lowered in individuals with germline PKD1 mutations. A label−free mass spectrometry comparison of urinary PKD−ELVs from normal individuals and those with PKD1 mutations showed that several proteins were reduced to a degree that matched the decrease observed in PC1 levels. Some of these proteins, such as polycystin-2 (PC2), may be present in a higher-order multi-protein assembly with PC1—the polycystin complex (PCC). CU062 (Q9NYP8) is decreased in ADPKD PKD−ELVs and, thus, is a candidate PCC component. CU062 is a small glycoprotein with a signal peptide but no transmembrane domain and can oligomerize with itself and interact with PC1. We investigated the localization of CU062 together with PC1 and PC2 using immunofluorescence (IF). In nonconfluent cells, all three proteins were localized in close proximity to focal adhesions (FAs), retraction fibers (RFs), and RF-associated extracellular vesicles (migrasomes). In confluent cells, primary cilia had PC1/PC2/CU062 + extracellular vesicles adherent to their plasma membrane. In cells exposed to mitochondrion-decoupling agents, we detected the development of novel PC1/CU062 + ring-like structures that entrained swollen mitochondria. In contact-inhibited cells under mitochondrial stress, PC1, PC2, and CU062 were observed on large, apically budding extracellular vesicles, where the proteins formed a reticular network on the membrane. CU062 interacts with PC1 and may have a role in the identification of senescent mitochondria and their extrusion in extracellular vesicles.
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