MEGF10 functions as a receptor for the uptake of amyloid-β

Thoudam Debraj Singh, Seung Yoon Park, Jae sung Bae, Youngeun Yun, Yong Chul Bae, Rang Woon Park, In San Kim

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

MEGF10 is predominantly expressed in the brain and known to function as a phagocytic receptor. Here, we provide evidence that MEGF10 is involved in the uptake of amyloid-β peptide (Aβ42) in the brain. Overexpression of MEGF10 dramatically increased Aβ42 uptake in Hela cells. Knockdown of endogenous MEGF10 expression significantly decreased Aβ42 uptake in N2A neuroblastoma cells. MEGF10-mediated Aβ uptake is mostly dependent on lipid raft endocytosis pathway. Furthermore, site-directed mutagenesis revealed that the conserved cytoplasmic NPxY and YxxØ motifs are crucial for MEGF10-mediated uptake of Aβ42 peptide. Thus, the identification of the MEGF10 as a functional receptor that mediates the uptake of amyloid-β peptide will help elucidate the molecular mechanisms of amlyoid-β clearance in Alzheimer's disease. Structured summary: MINT- 7993537: ctxB (uniprotkb:. P01556) and Abeta (uniprotkb:. P05067) colocalize (MI:. 0403) by fluorescence microscopy (MI:. 0416).

Original languageEnglish
Pages (from-to)3936-3942
Number of pages7
JournalFEBS Letters
Volume584
Issue number18
DOIs
Publication statusPublished - 2010 Sep
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Amyloid-β
  • Endocytosis
  • Lipid raft pathway
  • MEGF10

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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