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INVITED REVIEW

The kidney in vitamin B₁₂ and folate homeostasis: characterization of receptors for tubular uptake of vitamins and carrier proteins

Department of Cell Biology, Institute of Anatomy, University of Aarhus, Aarhus, Denmark

Over the past 10 years, animal studies have uncovered the molecular mechanisms for the renal tubular recovery of filtered vitamin and vitamin carrier proteins. Relatively few endocytic receptors are responsible for the proximal tubule uptake of a number of different vitamins, preventing urinary losses. In addition to vitamin conservation, tubular uptake by endocytosis is important to vitamin metabolism and homeostasis. The present review focuses on the receptors involved in renal tubular recovery of folate, vitamin B₁₂, and their carrier proteins. The multiligand receptor megalin is important for the uptake and tubular accumulation of vitamin B₁₂. During vitamin load, the kidney accumulates large amounts of free vitamin B₁₂, suggesting a possible storage function. In addition, vitamin B₁₂ is metabolized in the kidney, suggesting a role in vitamin homeostasis. The folate receptor is important for the conservation of folate, mediating endocytosis of the vitamin. Interaction between the structurally closely related, soluble folate-binding protein and megalin suggests that megalin plays an additional role in the uptake of folate bound to filtered folate-binding protein. A third endocytic receptor, the intrinsic factor-B₁₂ receptor cubilin-amnionless complex, is essential to the renal tubular uptake of albumin, a carrier of folate. In conclusion, uptake is mediated by interaction with specific endocytic receptors also involved in the renal uptake of other vitamins and vitamin carriers. Little is known about the mechanisms regulating intracellular transport and release of vitamins, and whereas tubular uptake is a constitutive process, this may be regulated, e.g., by vitamin status.

megalin; cubilin; folate-binding protein; proximal tubule; endocytosis

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