Myeloma light chains are ligands for cubilin (gp280)
Myeloma light chains are ligands for cubilin (gp280)
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DOI：
10.1152/ajprenal.1998.275.2.f246
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发表时间：
1998-08-01
影响因子：
4.2
通讯作者：
Hammond, TG
中科院分区：
文献类型：
--
作者：
Batuman, V;Verroust, PJ;Hammond, TG
虽然已知骨髓瘤轻链在肾脏中经历受体介导的内吞作用，但受体的分子身份尚未表征。我们检测了cubilin （gp280）与从多发性骨髓瘤患者尿液中分离的四种轻链之间的相互作用。四种证据表明cubilin是一种巨大的糖蛋白受体，它的分布局限于内噬清除途径，对内体运输有强大的影响，是一个潜在的生理相关的轻链结合位点：1)在cubilin的免疫亲和纯化过程中分离出的轻链；2)对cubilin而非对照血清的多克隆抗血清，取代了人轻链结合的大鼠肾刷缘膜；3)立方体在表面等离子体共振过程中与多种轻链结合；4)抗cubilin抗血清干扰内脏卵黄囊上皮细胞轻链内吞作用。然而，抗胆红素抗体只能部分抑制轻链与刷缘膜的结合以及卵黄囊上皮细胞对轻链的内吞作用，这表明存在其他或替代的轻链结合位点。过量轻链对体外内体融合有明显的抑制作用。结合表现出剂量和时间依赖的饱和性，具有低亲和力、高容量的平衡结合参数。这些数据表明，cubilin在肾近端小管细胞的内吞作用和轻链运输中起作用。
Although myeloma light chains are known to undergo receptor-mediated endocytosis in the kidney, the molecular identity of the receptor has not been characterized. We examined the interaction between cubilin (gp280) and four species of light chains isolated from the urine of patients with multiple myeloma. Four lines of evidence identify cubilin, a giant glycoprotein receptor, which is restricted in distribution to endocytic scavenger pathways and which has potent effects on endosomal trafficking, as a potentially physiologically relevant binding site for light chains: I) light chains coeluted during immunoaffinity purification of cubilin; 2) polyclonal antisera to cubilin but not control sera, displaced human light chain binding from rat renal brush-border membranes; 3) cubilin bound to multiple species of light chains during surface plasmon resonance; 4) anti-cubilin antiserum interfered with light chain endocytosis by visceral yolk sac epithelial cells. However, both binding of light chains to brush-border membranes and endocytosis of light chains by yolk sac epithelial cells were only partially inhibited by anticubilin antibodies, suggesting presence of additional or alternate binding sites for light chains. Excess light chain had a potent inhibitory effect on endosomal fusion in vitro. Binding showed dose and time-dependent saturability with low-affinity, high-capacity equilibrium binding parameters. These data demonstrate that cubilin plays a role in the endocytosis and trafficking of light chains in renal proximal tubule cells.