Renal reabsorption of folates from glomerular filtrate

Renal reabsorption of folates from glomerular filtrate in the proximal tubules under physiological conditions is thought to rely on the high-affinity folate receptor FRα through a process of transcytosis to the basolateral membrane into the blood. The multifunctional endocytic receptors megalin, which binds soluble folate binding proteins (FBP), and cubilin, which binds albumin (ALB), may also be involved in the uptake of folates under conditions of folate deficiency. The folate-specific transporters reduced folate carrier (RFC) and proton-coupled folate transported (PCFT) are highly expressed in the proximal renal tubule, with known expression of RFC at the basolateral membrane. Additional low-affinity, high-capacity folate transporters expressed at the apical membrane include the multidrug resistance-associated protein (MRP) efflux pumps 2 and 4 (MRP2 and MRP4) and the organic anion transporters (OAT) K1, K2, and 4. At the basolateral membrane, OAT1, OAT2, and OAT3 as well as the efflux pump MRP3 may contribute to renal folate transport.

Legend: ALB: albumin; FBP: folate binding protein; FRα: folate receptor alpha; MRP: multidrug resistance-associated protein; OAT: organic anion transporters; PCFT: proton-coupled folate transporter; RFC: reduced folate carrier. (Source: Shulpekova Y, Nechaev V, Kardasheva S, et al. The concept of folic acid in health and disease. Molecules 2021;26(12):3731.) (Modified by Dr. Douglas Lanska. Creative Commons Attribution 4.0 [CC BY] license.)