The amyloid precursor protein is a conserved Wnt receptor.

Autor:	Liu T; Paris Brain Institute - Institut du Cerveau, Sorbonne Université, Inserm, CNRS, Hôpital Pitié-Salpêtrière, Paris, France.; Doctoral School of Biomedical Sciences, Leuven, Belgium., Zhang T; Paris Brain Institute - Institut du Cerveau, Sorbonne Université, Inserm, CNRS, Hôpital Pitié-Salpêtrière, Paris, France.; Doctoral School of Biomedical Sciences, Leuven, Belgium., Nicolas M; Doctoral School of Biomedical Sciences, Leuven, Belgium.; Center for Brain and Disease, Leuven, Belgium.; Center for Human Genetics, University of Leuven School of Medicine, Leuven, Belgium., Boussicault L; Paris Brain Institute - Institut du Cerveau, Sorbonne Université, Inserm, CNRS, Hôpital Pitié-Salpêtrière, Paris, France., Rice H; Center for Brain and Disease, Leuven, Belgium.; Center for Human Genetics, University of Leuven School of Medicine, Leuven, Belgium., Soldano A; Center for Brain and Disease, Leuven, Belgium.; Center for Human Genetics, University of Leuven School of Medicine, Leuven, Belgium., Claeys A; Center for Brain and Disease, Leuven, Belgium.; Center for Human Genetics, University of Leuven School of Medicine, Leuven, Belgium., Petrova I; Laboratory of Developmental Neurobiology, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, Netherlands., Fradkin L; Laboratory of Developmental Neurobiology, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, Netherlands., De Strooper B; Center for Brain and Disease, Leuven, Belgium.; UK Dementia Research institute at University College London, London, United Kingdom., Potier MC; Paris Brain Institute - Institut du Cerveau, Sorbonne Université, Inserm, CNRS, Hôpital Pitié-Salpêtrière, Paris, France., Hassan BA; Paris Brain Institute - Institut du Cerveau, Sorbonne Université, Inserm, CNRS, Hôpital Pitié-Salpêtrière, Paris, France.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2021 Sep 09; Vol. 10. Date of Electronic Publication: 2021 Sep 09.
DOI:	10.7554/eLife.69199
Abstrakt:	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. Competing Interests: TL, TZ, MN, LB, HR, AS, AC, IP, LF, BD, MP, BH No competing interests declared (© 2021, Liu et al.)
Databáze:	MEDLINE
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