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).
Bibliographical noteFunding Information:
This study was supported by the Grant No. RTI04-01-01 from the Regional Technology Innovation Program of the Ministry of Knowledge Economy ; by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (No. R11-2008-044-03001-0 ); by WCU (World Class University) program through the Korea Science and Engineering Foundation funded by the Ministry of Education, Science and Technology ( R33-2008-000-10054-0 ); and by the Brain Korea 21 Project.
- Alzheimer's disease
- Lipid raft pathway
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology
- Cell Biology