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

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2 Citations (Scopus)


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 languageEnglish
Pages (from-to)206-212
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - Jul 22 2015



  • Dab2
  • Endocytosis
  • Megalin
  • Methylmolonic acid
  • Vitamin B<inf>12</inf>

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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