Mieszczanek, J., Strutt, H. orcid.org/0000-0003-4365-2271, Rutherford, T.J. et al. (3 more authors) (2022) Selective function of the PDZ domain of Dishevelled in noncanonical Wnt signalling. Journal of Cell Science, 135 (11). jcs259547. ISSN 0021-9533
Abstract
Dishevelled is a cytoplasmic hub that transduces Wnt signals to cytoplasmic effectors, which can be broadly characterised as canonical (β-catenin dependent) and noncanonical, to specify cell fates and behaviours during development. To transduce canonical Wnt signals, Dishevelled binds to the intracellular face of Frizzled through its DEP domain and polymerises through its DIX domain to assemble dynamic signalosomes. Dishevelled also contains a PDZ domain, whose function remains controversial. Here, we use genome editing to delete the PDZ domain-encoding region from Drosophila dishevelled. Canonical Wingless signalling is entirely normal in these deletion mutants; however, they show defects in multiple contexts controlled by noncanonical Wnt signalling, such as planar polarity. We use nuclear magnetic resonance spectroscopy to identify bona fide PDZ-binding motifs at the C termini of different polarity proteins. Although deletions of these motifs proved aphenotypic in adults, we detected changes in the proximodistal distribution of the polarity protein Flamingo (also known as Starry night) in pupal wings that suggest a modulatory role of these motifs in polarity signalling. We also provide new genetic evidence that planar polarity relies on the DEP-dependent recruitment of Dishevelled to the plasma membrane by Frizzled.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2022. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
Keywords: | Dishevelled; PDZ domain; Noncanonical Wnt signalling; Planar cell polarity; Drosophila |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) |
Funding Information: | Funder Grant number WELLCOME TRUST (THE) 210630/Z/18/Z WELLCOME TRUST (THE) 100986/Z/13/Z |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 17 Jun 2022 12:27 |
Last Modified: | 10 Feb 2023 14:13 |
Status: | Published |
Publisher: | The Company of Biologists |
Refereed: | Yes |
Identification Number: | 10.1242/jcs.259547 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:188111 |