Expression of insulin-like growth factor (IGF)-I receptors, IGF-II/cation-independent mannose 6-phosphate receptors (CI-MPRs), and cation-dependent MPRs in polarized human intestinal Caco-2 cells

We have analyzed the surface distribution and functional expression of the insulin-like growth factor I (IGF-I) receptor and the IGF-II/cation-independent mannose 6-phosphate receptor (IGF-II/CI-MPR) in the polarized human colon adenocarcinoma cell line, Caco-2. Domain-selective biotinylation of the apical and basolateral surfaces of Caco-2 cells grown on filter supports revealed a 3-4-fold enrichment of these receptors on basolateral membranes. In addition, the biotinylation studies revealed the presence of the cation-dependent MPR on both membrane surfaces, with a 3.4-fold enrichment on basolateral membranes. Binding of I-125-IGF-I at 4 degrees C confirmed similar higher levels of expression of the IGF-I receptor at the basolateral surface than at the apical surface. Cell surface-specific binding of the iodinated lysosomal enzyme beta-glucuronidase was detected at 4 degrees C on both plasma membrane domains. However, significant uptake of beta-glucuronidase at 37 degrees C was observed only from the basolateral surface. These results indicate that the MPRs and the IGF-I receptor are expressed in a polarized fashion in Caco-2 cells and that the IGFII/CI-MPR present on apical membranes, unlike the IGF-II/CI-MPR expressed on the basolateral surface, is not functional in endocytosing lysosomal enzymes.