title: Elevation of urinary methylmolonic acid induces the suppression of megalin-mediated endocytotic cycles during vitamin B12 deficiency.
abstract: Megalin is a scavenger receptor that serves in the endocytosis of a highly diverse group of ligands that includes Vitamin B12. We found an accumulation of megalin closed to apical region in renal proximal tubule cells of Vitamin B12-deficient rats. Interestingly, Vitamin B12 levels also controlled resorption of renal retinol binding protein. Using L2 yolk sac cells, megalin localized to the submembrane compartment by methylmalonic acid (MMA), which accumulates during vitamin B12 deficiency. In addition, MMA inhibited megalin-mediated endocytosis via YWTD repeats motif in an ectodomain of megalin. Therefore, megalin endocytosis may be regulated by MMA.
authors.affiliation: Department of Applied Biology and Chemistry, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shiga
authors.affiliation: Division of Life, Health, and Sports Education, Graduate School of Education, Okayama University, Okayama, Japan.
authors.forename: Tetsunori
authors.initials: T
authors.lastname: Kawata
authors.affiliation: Department of Nutrition, Junior College of Tokyo University of Agriculture, Tokyo, Japan.
authors.forename: Tadasu
authors.initials: T
authors.lastname: Furusho
authors.affiliation: Department of Applied Biology and Chemistry, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo, Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Tadokoro
authors.affiliation: Department of Applied Biology and Chemistry, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Applied Biology and Chemistry, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D000833:Animals, Suckling; D002460:Cell Line; D004705:Endocytosis; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000503:physiopathology; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics / Q000378:metabolism*; D008764:Methylmalonic Acid / Q000494:pharmacology / Q000652:urine*; D051381:Rats; D017208:Rats, Wistar; D012177:Retinol-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014805:Vitamin B 12 / Q000378:metabolism*; D014806:Vitamin B 12 Deficiency / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015017:Yolk Sac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D026561:Low Density Lipoprotein Receptor-Related Protein-2; D012177:Retinol-Binding Proteins; D008764:Methylmalonic Acid; D014805:Vitamin B 12
keywords: Dab2; Endocytosis; Megalin; Methylmolonic acid; Vitamin B(12)