Distinct functions of megalin and cubilin receptors in recovery of normal and nephrotic levels of filtered albumin.

ABSTRACT: Proximal tubule (PT) cells express a single saturable albumin-binding site whose affinity matches the estimated tubular concentration of albumin; however, albumin uptake capacity is greatly increased under nephrotic conditions. Deciphering the individual contributions of megalin and cubilin to the uptake of normal and nephrotic levels of albumin is impossible in vivo, as knockout of megalin in mice globally disrupts PT endocytic uptake. We quantified concentration-dependent albumin uptake in an optimized opossum kidney cell culture model and fit the kinetic profiles to identify albumin-binding affinities and uptake capacities. Mathematical deconvolution fit best to a three-component model that included saturable high- and low-affinity uptake sites for albumin and underlying nonsaturable up

SUBMITTER: Ren Q 

PROVIDER: S-EPMC7294330 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature