Geng L, Segal Y, Peissel B, Deng N, Pei Y, Carone F, Rennke H G, Glücksmann-Kuis A M, Schneider M C, Ericsson M, Reeders S T, Zhou J
Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Clin Invest. 1996 Dec 15;98(12):2674-82. doi: 10.1172/JCI119090.
Polycystin, the product of autosomal dominant polycystic kidney disease (ADPKD) 1 gene (PKD1) is the cardinal member of a novel class of proteins. As a first step towards elucidating the function of polycystin and the pathogenesis of ADPKD, three types of information were collected in the current study: the subcellular localization of polycystin, the spatial and temporal distribution of the protein within normal tissues and the effects of ADPKD mutations on the pattern of expression in affected tissues. Antisera directed against a synthetic peptide and two recombinant proteins of different domains of polycystin revealed the presence of an approximately 400-kD protein (polycystin) in the membrane fractions of normal fetal, adult, and ADPKD kidneys. Immunohistological studies localized polycystin to renal tubular epithelia, hepatic bile ductules, and pancreatic ducts, all sites of cystic changes in ADPKD, as well as in tissues such as skin that are not known to be affected in ADPKD. By electron microscopy, polycystin was predominantly associated with plasma membranes. Polycystin was significantly less abundant in adult than in fetal epithelia. In contrast, polycystin was overexpressed in most, but not all, cysts in ADPKD kidneys.
多囊蛋白是常染色体显性遗传性多囊肾病（ADPKD）1基因（PKD1）的产物，是一类新型蛋白质的主要成员。作为阐明多囊蛋白功能和ADPKD发病机制的第一步，本研究收集了三类信息：多囊蛋白的亚细胞定位、该蛋白在正常组织中的时空分布以及ADPKD突变对受累组织中表达模式的影响。针对多囊蛋白不同结构域的合成肽和两种重组蛋白制备的抗血清显示，在正常胎儿、成人及ADPKD肾脏的膜组分中存在一种约400-kD的蛋白质（多囊蛋白）。免疫组织学研究将多囊蛋白定位于肾小管上皮、肝胆小管和胰管，这些都是ADPKD中出现囊性改变的部位，以及如皮肤等已知不受ADPKD影响的组织。通过电子显微镜观察，多囊蛋白主要与质膜相关。多囊蛋白在成人上皮中的丰度明显低于胎儿上皮。相反，多囊蛋白在ADPKD肾脏的大多数（但不是全部）囊肿中过度表达。
