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

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-beta peptide (A beta 42) in the brain. Overexpression of MEGF10 dramatically increased A beta 42 uptake in Hela cells. Knockdown of endogenous MEGF10 expression significantly decreased A beta 42 uptake in N2A neuroblastoma cells. MEGF10-mediated A beta uptake is mostly dependent on lipid raft endocytosis pathway. Furthermore, site-directed mutagenesis revealed that the conserved cytoplasmic NPxY and YxxO motifs are crucial for MEGF10-mediated uptake of A beta 42 peptide. Thus, the identification of the MEGF10 as a functional receptor that mediates the uptake of amyloid-beta peptide will help elucidate the molecular mechanisms of amlyoid-beta clearance in Alzheimer's disease. Structured summary: MINT-7993537: ctxB (uniprotkb:P01556) and Abeta (uniprotkb:P05067) colocalize (MI:0403) by fluorescence microscopy (MI:0416) (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.