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-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.
Singh
Thoudam Debraj
TD
Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Park
Seung-Yoon
SY
Bae
Jae-sung
JS
Yun
Youngeun
Y
Bae
Yong-Chul
YC
Park
Rang-Woon
RW
Kim
In-San
IS
D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism; D017124:Conserved Sequence; D004705:Endocytosis; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*
D016229:Amyloid beta-Peptides; C522055:MEGF10, human; D008565:Membrane Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D002784:Cholesterol