Liu, T;
Zhang, T;
Nicolas, M;
Boussicault, L;
Rice, H;
Soldano, A;
Claeys, A;
... Hassan, BA; + view all
(2021)
The amyloid precursor protein is a conserved Wnt receptor.
eLife
, 10
, Article e69199. 10.7554/eLife.69199.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | The amyloid precursor protein is a conserved Wnt receptor |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.7554/eLife.69199 |
| Publisher version: | https://doi.org/10.7554/eLife.69199 |
| Language: | English |
| Additional information: | © Liu et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UK Dementia Research Institute HQ |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10135381 |
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