Nagano Junko, Kitamura Kenichiro, Hujer Kristine M, Ward Christopher J, Bram Richard J, Hopfer Ulrich, Tomita Kimio, Huang Chunfa, Miller R Tyler
Division of Nephrology, Department of Medicine, Case Western Reserve University, Lois Stokes Veterans Affairs Medical Center, Cleveland, OH, USA.
Biochem Biophys Res Commun. 2005 Dec 16;338(2):880-9. doi: 10.1016/j.bbrc.2005.10.022. Epub 2005 Oct 14.
The predicted structure of the autosomal recessive polycystic kidney disease protein, fibrocystin, suggests that it may function as a receptor, but its function remains unknown. To understand its function, we searched for proteins that interact with the intracellular C-terminus of fibrocystin using the yeast two-hybrid system. From the screening, we found calcium modulating cyclophilin ligand (CAML), a protein involved in Ca(2+) signaling. Immunofluorescent analysis showed that both proteins are co-localized in the apical membrane, primary cilia, and the basal body of cells derived from the distal nephron Epitope-tagged expression constructs of both proteins were co-immunoprecipitated from COS7 cells. The intracellular C-terminus of fibrocystin interacts with CAML, a protein with an intracellular distribution that is similar to that of PKD2. Fibrocystin may participate in regulation of intracellular Ca(2+) in the distal nephron in a manner similar to PKD1 and PKD2 that are involved in autosomal dominant polycystic kidney disease.
常染色体隐性多囊肾病蛋白纤维囊素的预测结构表明它可能作为一种受体发挥作用，但其功能仍然未知。为了解其功能，我们利用酵母双杂交系统寻找与纤维囊素细胞内C末端相互作用的蛋白质。通过筛选，我们发现了钙调节亲环蛋白配体（CAML），一种参与Ca(2+)信号传导的蛋白质。免疫荧光分析表明，这两种蛋白质共定位于远曲小管来源细胞的顶膜、初级纤毛和基体。两种蛋白质的表位标记表达构建体从COS7细胞中共免疫沉淀。纤维囊素的细胞内C末端与CAML相互作用，CAML是一种细胞内分布与多囊蛋白2（PKD2）相似的蛋白质。纤维囊素可能以类似于参与常染色体显性多囊肾病的多囊蛋白1（PKD1）和PKD2的方式参与远曲小管细胞内Ca(2+)的调节。
