Transcobalamin II receptor interacts with megalin in the renal apical brush border membrane. J Membr Biol 2003 May 01;193(1):57-66
Date
07/25/2003Pubmed ID
12879166DOI
10.1007/s00232-002-2007-3Scopus ID
2-s2.0-0041624141 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
Purified human transcobalamin II receptor (TC II-R) binds to megalin, a 600 kDa endocytic receptor with an association constant, K(a), of 66 n M and bound(max) of 1.1 mole of TC II-R/mole of megalin both in the presence and absence of its ligand, transcobalamin II (TC II). Immunoprecipitation followed by immunoblotting of Triton X-100 extracts of the apical brush border membrane (BBM) from rabbit renal cortex revealed association of these two proteins. (35)[S]-TC II complexed with cobalamin (Cbl; Vitamin B(12)) bound to Sepharose-megalin affinity matrix and the binding was enhanced 5-fold when TC II-R was prebound to megalin. Megalin antiserum inhibited both the TC II-R-dependent and -independent binding of (35)[S]-TC II-Cbl to megalin, while TC II-R antiserum inhibited only the TC II-R-dependent binding. In rabbits with circulating antiserum to megalin, renal apical BBM megalin was present as an immune complex, but its levels were not altered. However, the protein levels of both TC II-R and the cation-independent mannose 6-phosphate receptor (CIMPR) were drastically reduced and the urinary excretion of TC II, albumin, and other low-molecular weight proteins was significantly increased. These results suggest that megalin contains a distinct single high-affinity binding site for TC II-R and their association in the native renal BBM is important for tubular reabsorption of many proteins, including TC II.
Author List
Yammani RR, Seetharam S, Dahms NM, Seetharam BAuthor
Nancy M. Dahms PhD Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Membrane
Cells, Cultured
Intestinal Mucosa
Kidney
Low Density Lipoprotein Receptor-Related Protein-2
Microvilli
Protein Binding
Rabbits
Receptors, Cell Surface
Transcobalamins