Cubilin is an albumin binding protein important for renal tubular albumin reabsorption
Cubilin is an albumin binding protein important for renal tubular albumin reabsorption
复制标题
DOI：
10.1172/jci8862
复制
发表时间：
2000-05-01
影响因子：
15.9
通讯作者：
Christensen, EI
中科院分区：
文献类型：
--
作者：
Birn, H;Fyfe, JC;Christensen, EI
使用亲和层析和表面等离子体共振分析，我们已经确定cubilin，460 kDa的受体大量表达在肾近端小管上皮细胞，作为白蛋白结合蛋白。具有cubilin功能缺陷的犬排泄大量白蛋白，同时几乎消除了近端小管重吸收，表明cubilin在近端小管吸收白蛋白中起关键作用。此外，通过免疫印迹和免疫细胞化学，我们表明，以前确定的低分子量肾白蛋白结合蛋白的cubilin片段。此外，我们发现缺乏内吞受体megalin的小鼠显示尿排泄改变，肾小管重吸收减少，白蛋白。由于cubilin已被证明与megalin共定位和相互作用，我们提出了一种由这两种蛋白质介导的白蛋白重吸收机制。这一过程可能对理解近端小管吸收增加的滤过白蛋白负荷引起的间质性肾炎症和纤维化很重要。
Using affinity chromatography and surface plasmon resonance analysis, we have identified cubilin, a 460-kDa receptor heavily expressed in kidney proximal tubule epithelial cells, as an albumin binding protein. Dogs with a functional defect in cubilin excrete large amounts of albumin in combination with virtually abolished proximal tubule reabsorption, showing the critical role for cubilin in the uptake of albumin by the proximal tubule. Also, by immunoblotting and immunocytochemistry we show that previously identified low-molecular-weight renal albumin binding proteins are fragments of cubilin. In addition, we find that mice lacking the endocytic receptor megalin show altered urinary excretion, and reduced tubular reabsorption, of albumin. Because cubilin has been shown to colocalize and interact with megalin, we propose a mechanism of albumin reabsorption mediated by both of these proteins. This process may prove important for understanding interstitial renal inflammation and fibrosis caused by proximal tubule uptake of an increased load of filtered albumin.