Endocytic Receptors in the Renal Proximal Tubule

Abstract

Protein reabsorption is a predominant feature of the renal proximal tubule. Animal studies show that the ability to rescue plasma proteins relies on the endocytic receptors megalin and cubilin. Recently, studies of patients with syndromes caused by dysfunctional receptors have supported the importance of these for protein clearance of human ultrafiltrate. This review focuses on the molecular biology and physiology of the receptors and their involvement in renal pathological conditions.

Effect of Type 2 Diabetes Mellitus and Diabetic Nephropathy on IgG Pharmacokinetics and Subcutaneous Bioavailability in the Rat

“…These are co-expressed in several absorptive epithelia, small intestine and renal proximal tubule. Megalin is more widely distributed than cubilin and is expressed in glomerular podocytes as well (43). Megalin and cubilin function together in the reabsorption of proteins, including IgG and albumin, in the proximal tubule (43,44).…”

“…Megalin is more widely distributed than cubilin and is expressed in glomerular podocytes as well (43). Megalin and cubilin function together in the reabsorption of proteins, including IgG and albumin, in the proximal tubule (43,44). Impairment of megalin function in diabetes has been suggested, even in the early stages of diabetes in animal models and in patients (45).…”

“…Pioglitazone at low doses, even without glycemic control, normalizes the renal levels of TNF-α and megalin (47). Thus, impaired renal expression of megalin may not only inhibit the clearance of IgG antibodies from glomerular podocytes (thus causing local inflammation and glomerular damage), but also prevent the uptake and catabolism of IgG through the proximal tubule cells (43). During protein overload in diseases like T2DM, these receptors would mediate uptake of surplus protein for accumulation in lysosomes.…”

Mapping the Binding Region on the Low Density Lipoprotein Receptor for Blood Coagulation Factor VIII

“…Most likely, this was due to blocking of LDLR by RAP, and not other RAP-sensitive determinants. Among them, VLDLR (expressed in endothelium) does not contribute to FVIII clearance in mice (15); also, such a role of megalin cannot be justified due to its location in the renal proximal tubule, accessible only to small plasma ligands (16). In turn, upon injection of […”

“…Two other receptors from the family, very low density lipoprotein receptor (VLDLR) and megalin, are also found in the circulation. Although both receptors bind to FVIII in a purified system (13,14), they are likely not involved in its clearance in vivo (15,16).…”