La Trobe

sorry, we can't preview this file

Drosophila melanogaster Guk-holder and Scribbled PDZ1 domain and Scribbled and Discs Large.pdf (3.51 MB)

Drosophila melanogaster Guk-holder interacts with the Scribbled PDZ1 domain and regulates epithelial development with Scribbled and Discs Large

Download (3.51 MB)
journal contribution
posted on 29.01.2021, 03:40 by Sofia Caria, Charlene Magtoto, Tinaz Samiei, Marta Portela-Esteban, Krystle Lim, Jing Yuan How, Bryce Stewart, Patrick Humbert, Helena Richardson, Marc Kvansakul
© 2018 by The American Society for Biochemistry and Molecular Biology, Inc. Epithelial cell polarity is controlled by components of the Scribble polarity module, and its regulation is critical for tissue architecture and cell proliferation and migration. In Drosophila melanogaster, the adaptor protein Guk-holder (Gukh) binds to the Scribbled (Scrib) and Discs Large (Dlg) components of the Scribble polarity module and plays an important role in the formation of neuromuscular junctions. However, Gukh’s role in epithelial tissue formation and the molecular basis for the Scrib–Gukh interaction remain to be defined. We now show using isothermal titration calorimetry that the Scrib PDZ1 domain is the major site for an interaction with Gukh. Furthermore, we defined the structural basis of this interaction by determining the crystal structure of the Scrib PDZ1–Gukh complex. The C-terminal PDZ-binding motif of Gukh is located in the canonical ligand-binding groove of Scrib PDZ1 and utilizes an unusually extensive network of hydrogen bonds and ionic interactions to enable binding to PDZ1 with high affinity. We next examined the role of Gukh along with those of Scrib and Dlg in Drosophila epithelial tissues and found that Gukh is expressed in larval-wing and eye-epithelial tissues and co-localizes with Scrib and Dlg at the apical cell cortex. Importantly, we show that Gukh functions with Scrib and Dlg in the development of Drosophila epithelial tissues, with depletion of Gukh enhancing the eye- and wing-tissue defects caused by Scrib or Dlg depletion. Overall, our findings reveal that Scrib’s PDZ1 domain functions in the interaction with Gukh and that the Scrib–Gukh interaction has a key role in epithelial tissue development in Drosophila.

History

Publication Date

23/03/2018

Journal

Journal of Biological Chemistry

Volume

293

Issue

12

Pagination

13p. (p. 4519-4531)

Publisher

American Society for Biochemistry and Molecular Biology

ISSN

1083-351X

Rights Statement

The Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.

Licence

Exports