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

作者：Singh Thoudam Debraj; Park Seung Yoon; Bae Jae Sung; Yun Youngeun; Bae Yong Chul; Park Rang Woon; Kim In San^*

来源：FEBS Letters, 2010, 584(18): 3936-3942.

DOI：10.1016/j.febslet.2010.08.050

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

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 (uniprotk

• 出版日期2010-9-24