The Drosophila homologue of the amyloid precursor protein is a conserved modulator of Wnt PCP signaling.

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Authors

SOLDANO Alessia OKRAY Zeynep JANOVSKÁ Pavlína TMEJOVÁ Kateřina REYNAUD Elodie CLAEYS Annelies YAN Jiekun ATAK Zeynep Kalender DE STROOPER Bart DURA Jean-Maurice BRYJA Vítězslav HASSAN Bassem A.

Year of publication 2013
Type Article in Periodical
Magazine / Source PLoS Biology
MU Faculty or unit

Faculty of Science

Citation
Web http://apps.webofknowledge.com/full_record.do?product=UA&search_mode=GeneralSearch&qid=1&SID=X1Amd9VvQGafBKx7B2c&page=1&doc=1
Doi http://dx.doi.org/10.1371/journal.pbio.1001562
Field Genetics and molecular biology
Keywords PLANAR CELL POLARITY; ALZHEIMERS-DISEASE; AXONAL-TRANSPORT; FAMILY-MEMBERS; DEFICIENT MICE; GENE; APP; HYPOTHESIS; NEURON; THERAPEUTICS
Description Wnt Planar Cell Polarity (PCP) signaling is a universal regulator of polarity in epithelial cells, but it regulates axon outgrowth in neurons, suggesting the existence of axonal modulators of Wnt-PCP activity. The Amyloid precursor proteins (APPs) are intensely investigated because of their link to Alzheimer's disease (AD). APP's in vivo function in the brain and the mechanisms underlying it remain unclear and controversial. Drosophila possesses a single APP homologue called APP Like, or APPL. APPL is expressed in all neurons throughout development, but has no established function in neuronal development. We therefore investigated the role of Drosophila APPL during brain development. We find that APPL is involved in the development of the Mushroom Body alfa beta neurons and, in particular, is required cell-autonomously for the beta-axons and non-cell autonomously for the alfa-axons growth. Moreover, we find that APPL is a modulator of the Wnt-PCP pathway required for axonal outgrowth, but not cell polarity. Molecularly, both human APP and fly APPL form complexes with PCP receptors, thus suggesting that APPs are part of the membrane protein complex upstream of PCP signaling. Moreover, we show that APPL regulates PCP pathway activation by modulating the phosphorylation of the Wnt adaptor protein Dishevelled (Dsh) by Abelson kinase (Abl). Taken together our data suggest that APPL is the first example of a modulator of the Wnt-PCP pathway specifically required for axon outgrowth.
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