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Published on: October 17, 2015
MEGF10 functions as a receptor for the uptake of amyloid-β
Thoudam Debraj Singh1, Seung-Yoon Park, Jae-sung Bae
1Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
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.
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