Publication detail

The Drosophila Homologue of the Amyloid Precursor Protein Is a Conserved Modulator of Wnt PCP Signaling

Soldano, A. Okray, Z. Janovska, P. Tmejova, K. Reynaud, E. Claeys, A. Yan, JK. Atak, ZK. De Strooper, B. Dura, JM. Bryja, V. Hassan, BA

Original Title

The Drosophila Homologue of the Amyloid Precursor Protein Is a Conserved Modulator of Wnt PCP Signaling

Type

journal article in Web of Science

Language

English

Original Abstract

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 alpha beta neurons and, in particular, is required cell-autonomously for the beta-axons and non-cell autonomously for the alpha-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.

Keywords

PLANAR CELL POLARITY; ALZHEIMERS-DISEASE; AXONAL-TRANSPORT; FAMILY-MEMBERS; DEFICIENT MICE ;GENE; APP; HYPOTHESIS; NEURON; THERAPEUTICS

Authors

Soldano, A.; Okray, Z.; Janovska, P.; Tmejova, K.; Reynaud, E.; Claeys, A.; Yan, JK.; Atak, ZK.; De Strooper, B.; Dura, JM.; Bryja, V.; Hassan, BA

Released

1. 5. 2013

ISBN

1544-9173

Periodical

PLOS BIOLOGY

Year of study

11

Number

5

State

United States of America

Pages from

1

Pages to

13

Pages count

13

URL

https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001562

BibTex

@article{BUT183285,
  author="Soldano, A. and Okray, Z. and Janovska, P. and Tmejova, K. and Reynaud, E. and Claeys, A. and Yan, JK. and Atak, ZK. and De Strooper, B. and Dura, JM. and Bryja, V. and Hassan, BA",
  title="The Drosophila Homologue of the Amyloid Precursor Protein Is a Conserved Modulator of Wnt PCP Signaling",
  journal="PLOS BIOLOGY",
  year="2013",
  volume="11",
  number="5",
  pages="1--13",
  doi="10.1371/journal.pbio.1001562",
  issn="1544-9173",
  url="https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001562"
}