First Author | Kaseda R | Year | 2007 |
Journal | Biochem Biophys Res Commun | Volume | 357 |
Issue | 4 | Pages | 1130-4 |
PubMed ID | 17462596 | Mgi Jnum | J:121774 |
Mgi Id | MGI:3711604 | Doi | 10.1016/j.bbrc.2007.04.072 |
Citation | Kaseda R, et al. (2007) Megalin-mediated endocytosis of cystatin C in proximal tubule cells. Biochem Biophys Res Commun 357(4):1130-4 |
abstractText | Serum levels of cystatin C, an endogenous cysteine proteinase inhibitor, are often used as an indicator of glomerular filtration rate. Although it is known that cystatin C is filtered by glomeruli and metabolized in proximal tubule cells (PTC), the precise molecular mechanism underlying this process is undetermined. Using quartz-crystal microbalance analyses, we demonstrate that cystatin C binds directly to megalin, an endocytic receptor in PTC, in a Ca(+)-dependent manner. We also find that cystatin C is endocytosed specifically via megalin in rat yolk sac epithelium-derived L2 cells which share a variety of characteristics with PTC. Finally, in vivo studies using kidney-specific megalin knockout mice provide evidence that megalin mediates proximal tubular uptake of cystatin C. We conclude that megalin is an endocytic receptor of cystatin C in PTC. |