Engulfment of Toxic Amyloid β-protein in Neurons and Astrocytes Mediated by MEGF10

•Neurons and astrocytes engulfed A β42 and A β43, which are more neurotoxic than A β40.•MEGF10-expressing astrocytes and neurons engulfed A β42 and A β43 but not A β40.•Neurons and astrocytes incubation with A β42 and A β43 augmented MEGF10 phosphorylation.•Incubation with A β40 did not have augment...

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Published in:Neuroscience 2020-09, Vol.443, p.1-7
Main Authors: Fujita, Yu, Maeda, Tomoji, Sato, Chiharu, Sato, Masaya, Hatakeyama, Hatsune, Ota, Yume, Iwabuchi, Nozomi, Tatesawa, Komaki, Nomura, Ayako, Zou, Kun, Komano, Hiroto
Format: Article
Language:English
Subjects:
Alzheimer Disease
Amyloid beta-Peptides - toxicity
amyloid-β protein
Animals
Astrocytes
draper
MEGF10
Membrane Proteins
Neurons
phagocytosis receptor
phosphorylation
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Summary:•Neurons and astrocytes engulfed A β42 and A β43, which are more neurotoxic than A β40.•MEGF10-expressing astrocytes and neurons engulfed A β42 and A β43 but not A β40.•Neurons and astrocytes incubation with A β42 and A β43 augmented MEGF10 phosphorylation.•Incubation with A β40 did not have augmenting effect.•MEGF10 plays a phagocytosis receptor function for A β42 and A β43 in neurons and astrocytes. Amyloid-β proteins (A β), including Aβ42 and A β 43, are known pathogenesis factors of Alzheimer’s disease (AD). Unwanted substances in the brain, including A β, are generally removed by microglia, astrocytes, or neurons via a phagocytosis receptor. We observed that neurons and astrocytes engulfed A β 42 and A β 43, which are more neurotoxic than A β 40. We previously showed that multiple-EGF like domains 10 (MEGF10) plays an important role in apoptotic cell elimination and is expressed in mammalian neurons and astrocytes. Therefore, we assessed whether MEGF10 is involved in A β42 and A β43 engulfment in MEGF10-expressing neurons and astrocytes. We found that MEGF10-expressing astrocytes and neurons engulfed A β42 and A β43 but not A β40. Furthermore, incubation of the neurons and astrocytes with A β42 and A β43a ugmented MEGF10 phosphorylation; however, incubation with A β40 did not have this augmenting effect. Our findings suggest that MEGF10 plays a phagocytosis receptor function for A β42 and A β43 in neurons and astrocytes.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2020.07.016