Megalin is essential for renal proximal tubule reabsorption and accumulation of transcobalamin-B-12

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Item Type:	Article
Title:	Megalin is essential for renal proximal tubule reabsorption and accumulation of transcobalamin-B-12
Creators Name:	Birn, H., Willnow, T.E., Nielsen, R., Norden, A.G.W., Boensch, C., Moestrup, S.K., Nexo, E. and Christensen, E.I.
Abstract:	Megalin has previously been shown to bind and mediate endocytosis of transcobalamin (TC)-B12. However, the physiological significance of this has not been established, and other TC-B12 binding proteins have been suggested to mediate renal uptake of this vitamin complex. The present study demonstrates by the use of megalin-deficient mice that megalin is, in fact, essential for the normal renal reabsorption of TC-vitamin B12 and for renal accumulation of this highly conserved vitamin. Megalin-deficient mice excrete increased amounts of TC and B12 in the urine, revealing a defective renal tubular uptake of TC-B12. The urinary B12 excretion is increased ∼4-fold, resulting in an ∼28-fold higher renal B12 clearance. This is associated with an ∼4-fold decrease in B12 content in megalin-deficient kidney cortex. Thus megalin is important to prevent urinary loss of vitamin B12. In addition, light- and electron-microscopic immunocytochemistry demonstrate lysosomal accumulation of B12 in rat and mouse proximal tubules. In rats this accumulation is correlated with vitamin intake. Thus renal lysosomal B12 accumulation is dependent on vitamin status, indicating a possible reserve function of this organelle in the rat kidney.
Keywords:	Cobalamin, Immunocytochemistry, Kidney, Lysosomes, Receptor-Mediated Endocytosis, Animals, Guinea Pigs, Mice, Rats
Source:	American Journal of Physiology Renal Physiology
ISSN:	0363-6127
Publisher:	American Physiological Society
Volume:	282
Number:	3
Page Range:	F408-F416
Date:	1 January 2002
Official Publication:	https://doi.org/10.1152/ajprenal.00206.2000
PubMed:	View item in PubMed

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