Publications

Publications Search

Search for publications by author
Search for publications by abstract keyword(s)

Shedding new light on RhoA signalling as a drug target in vivo using a novel RhoA-FRET biosensor mouse

Abstract

The small GTPase RhoA is a master regulator of signalling in cell-extracellular matrix interactions. RhoA signalling is critical to many cellular processes including migration, mechanotransduction, and is often disrupted in carcinogenesis. Investigating RhoA activity in a native tissue environment is challenging using conventional biochemical methods; we therefore developed a RhoA-FRET biosensor mouse, employing the adaptable nature of intravital imaging to a variety of settings. Mechanotransduction was explored in the context of osteocyte processes embedded in the calvaria responding in a directional manner to compression stress. Further, the migration of neutrophils was examined during in vivo "chemotaxis" in wound response. RhoA activity was tightly regulated during tissue remodelling in mammary gestation, as well as during mammary and pancreatic carcinogenesis. Finally, pharmacological inhibition of RhoA was temporally resolved by the use of optical imaging windows in fully developed pancreatic and mammary tumours in vivo. The RhoA-FRET mouse therefore constitutes a powerful tool to facilitate development of new inhibitors targeting the RhoA signalling axis.

Type Journal
ISBN 2154-1256 (Electronic) 2154-1248 (Linking)
Authors Nobis, M.; Herrmann, D.; Warren, S. C.; Strathdee, D.; Cox, T. R.; Anderson, K. I.; Timpson, P.
Responsible Garvan Author Professor Paul Timpson
Publisher Name Small GTPases
Published Date 2020-07-01
Published Volume 11
Published Issue 4
Published Pages 240-247
Status Published in-print
DOI 10.1080/21541248.2018.1438024
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/29457531