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

FEBS Lett. 2010 Sep 24;584(18):3936-42. doi: 10.1016/j.febslet.2010.08.050. Epub 2010 Sep 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Amino Acid Sequence
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Brain / metabolism*
  • Cell Line, Tumor
  • Cholesterol / metabolism
  • Conserved Sequence
  • Endocytosis
  • HeLa Cells
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Peptide Fragments / metabolism*

Substances

  • Amyloid beta-Peptides
  • MEGF10, human
  • Membrane Proteins
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • Cholesterol