Distribution of IGF receptors in the plasma membrane of proximal tubular cells

Abstract

To characterize the distribution of receptors for insulin-like growth factors I and II (IGF I and II) in the plasma membrane of the renal proximal tubular cell, we measured binding of 125I-labeled IGF I and 125I-labeled IGF II to proximal tubular basolateral and brush-border membranes and characterized IGF I-stimulated phosphorylation of detergent-solubilized membranes. 125I-IGF I bound primarily to a 135,000 relative molecular weight (Mr) protein and IGF II to a 260,000 Mr protein in isolated membranes. Binding of 125I-IGF I was severalfold greater in basolateral than in brush-border membranes. IGF I-stimulated phosphorylation of the 92,000 Mr beta-subunit of its receptor could be demonstrated only in basolateral membranes. These findings are consistent with an asymmetrical distribution of receptors for IGF I in the plasma membrane of the renal proximal tubular cell, localization being primarily on the basolateral side. In contrast, binding of 125I-IGF II to isolated basolateral and brush-border membranes was equivalent, suggesting that receptors for this peptide are distributed more symmetrically in the plasma membrane. Our findings suggest that the actions of IGF I in proximal tubule are mediated via interaction of circulating peptide with specific receptors in the basolateral membrane. However, our findings establish the potential for actions of IGF II to be exerted in proximal tubule via interaction with both basolateral and/or brush-border membrane receptors.