Elevation of urinary methylmolonic acid induces the suppression of megalin-mediated endocytotic cycles during Vitamin B12 deficiency

Takahiro Shiga; Tetsunori Kawata; Tadasu Furusho; Tadahiro Tadokoro; Tsukasa Suzuki; Yuji Yamamoto

doi:10.1016/j.bbrc.2015.07.151

Elevation of urinary methylmolonic acid induces the suppression of megalin-mediated endocytotic cycles during Vitamin B₁₂ deficiency

Takahiro Shiga, Tetsunori Kawata, Tadasu Furusho, Tadahiro Tadokoro, Tsukasa Suzuki, Yuji Yamamoto

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

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.

Original language	English
Pages (from-to)	206-212
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	465
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2015.07.151
Publication status	Published - Sept 18 2015

Keywords

Dab2
Endocytosis
Megalin
Methylmolonic acid
Vitamin B

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2015.07.151

Cite this

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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.",

keywords = "Dab2, Endocytosis, Megalin, Methylmolonic acid, Vitamin B",

author = "Takahiro Shiga and Tetsunori Kawata and Tadasu Furusho and Tadahiro Tadokoro and Tsukasa Suzuki and Yuji Yamamoto",

note = "Funding Information: The authors thank Kaori Ishida, Okayama University, Japan for technical support in the animal experiments. This work was supported by a NODAI Ph.D. Student Research Supporting Project Grant no. 46404707F from Tokyo University of Agriculture (Takahiro Shiga). Publisher Copyright: {\textcopyright} 2015 Published by Elsevier Inc.",

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AU - Shiga, Takahiro

AU - Kawata, Tetsunori

AU - Furusho, Tadasu

AU - Tadokoro, Tadahiro

AU - Suzuki, Tsukasa

AU - Yamamoto, Yuji

N1 - Funding Information: The authors thank Kaori Ishida, Okayama University, Japan for technical support in the animal experiments. This work was supported by a NODAI Ph.D. Student Research Supporting Project Grant no. 46404707F from Tokyo University of Agriculture (Takahiro Shiga). Publisher Copyright: © 2015 Published by Elsevier Inc.

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N2 - 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.

AB - 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.

KW - Dab2

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