The amyloid precursor protein is a conserved Wnt receptor.
Amino Acid Sequence
Amyloid beta-Protein Precursor
/ chemistry
Animals
Brain
/ cytology
Cells, Cultured
Cloning, Molecular
Drosophila Proteins
/ genetics
Drosophila melanogaster
Gene Deletion
Gene Expression Regulation
/ physiology
Humans
Membrane Proteins
/ genetics
Mice
Mushroom Bodies
/ cytology
Nerve Tissue Proteins
/ genetics
Neurons
/ metabolism
Protein Transport
Receptors, Wnt
/ genetics
Signal Transduction
D. melanogaster
Drosophila
alzheimer's disease
amyloid precursor protein
brain development
cell biology
mouse
neuroscience
wnt
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
09 09 2021
09 09 2021
Historique:
received:
09
04
2021
accepted:
01
09
2021
entrez:
13
9
2021
pubmed:
14
9
2021
medline:
28
10
2021
Statut:
epublish
Résumé
The Amyloid Precursor Protein (APP) and its homologues are transmembrane proteins required for various aspects of neuronal development and activity, whose molecular function is unknown. Specifically, it is unclear whether APP acts as a receptor, and if so what its ligand(s) may be. We show that APP binds the Wnt ligands Wnt3a and Wnt5a and that this binding regulates APP protein levels. Wnt3a binding promotes full-length APP (flAPP) recycling and stability. In contrast, Wnt5a promotes APP targeting to lysosomal compartments and reduces flAPP levels. A conserved Cysteine-Rich Domain (CRD) in the extracellular portion of APP is required for Wnt binding, and deletion of the CRD abrogates the effects of Wnts on flAPP levels and trafficking. Finally, loss of APP results in increased axonal and reduced dendritic growth of mouse embryonic primary cortical neurons. This phenotype can be cell-autonomously rescued by full length, but not CRD-deleted, APP and regulated by Wnt ligands in a CRD-dependent manner.
Identifiants
pubmed: 34515635
doi: 10.7554/eLife.69199
pii: 69199
pmc: PMC8437438
doi:
pii:
Substances chimiques
Amyloid beta-Protein Precursor
0
Appl protein, Drosophila
0
Drosophila Proteins
0
Membrane Proteins
0
Nerve Tissue Proteins
0
Receptors, Wnt
0
Vang protein, Drosophila
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2021, Liu et al.
Déclaration de conflit d'intérêts
TL, TZ, MN, LB, HR, AS, AC, IP, LF, BD, MP, BH No competing interests declared
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