Netrin-dependent downregulation of Frazzled/DCC is required for the dissociation of the peripodial epithelium in Drosophila

Rosemary Manhire-Heath, Sofia Golenkina, Robert Saint and Michael J. Murray ()
Additional contact information
Rosemary Manhire-Heath: University of Melbourne
Sofia Golenkina: University of Melbourne
Robert Saint: University of Melbourne
Michael J. Murray: University of Melbourne

Nature Communications, 2013, vol. 4, issue 1, 1-10

Abstract: Abstract Netrins are secreted chemoattractants with roles in axon guidance, cell migration and epithelial plasticity. Netrin-1 also promotes the survival of metastasized cells by inhibiting the pro-apoptotic effects of its receptor Deleted in Colorectal Carcinoma (DCC). Here we report that Netrins can also regulate epithelial dissociation during Drosophila wing eversion. During eversion, peripodial epithelial cells lose apico-basal polarity and adherens junctions, and become migratory and invasive—a process similar to an epithelial–mesenchymal transition. Loss of netrinA inhibits the breakdown of cell–cell junctions, leading to eversion failure. In contrast, the Netrin receptor Frazzled blocks eversion when overexpressed, whereas frazzled RNAi accelerates eversion in vitro. In peripodial cells Frazzled is endocytosed, and undergoes NetA-dependent degradation, which is required for eversion. Finally, we provide evidence that Frazzled acts through the ERM-family protein Moesin to inhibit eversion. This mechanism may also help explain the role of Netrin and DCC in cancer metastasis.

Date: 2013
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms3790 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3790

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms3790

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().