Publications

Publications Search

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

A RhoA-FRET biosensor mouse for intravital imaging in normal tissue homeostasis and disease contexts

Abstract

The small GTPase RhoA is involved in a variety of fundamental processes in normal tissue. Spatiotemporal control of RhoA is thought to govern mechanosensing, growth, and motility of cells, while its deregulation is associated with disease development. Here, we describe the generation of a RhoA-fluorescence resonance energy transfer (FRET) biosensor mouse and its utility for monitoring real-time activity of RhoA in a variety of native tissues in vivo. We assess changes in RhoA activity during mechanosensing of osteocytes within the bone and during neutrophil migration. We also demonstrate spatiotemporal order of RhoA activity within crypt cells of the small intestine and during different stages of mammary gestation. Subsequently, we reveal co-option of RhoA activity in both invasive breast and pancreatic cancers, and we assess drug targeting in these disease settings, illustrating the potential for utilizing this mouse to study RhoA activity in vivo in real time.

Type Journal
ISBN 2211-1247 (Electronic)
Authors Nobis, M.; Herrmann, D.; Warren, S. C.; Kadir, S.; Leung, W.; Killen, M.; Magenau, A.; Stevenson, D.; Lucas, M. C.; Reischmann, N.; Vennin, C.; Conway, J. R. W.; Boulghourjian, A.; Zaratzian, A.; Law, A. M.; Gallego-Ortega, D.; Ormandy, C. J.; Walters, S. N.; Grey, S. T.; Bailey, J.; Chtanova, T.; Quinn, J. M. W.; Baldock, P. A.; Croucher, P. I.; Schwarz, J. P.; Mrowinska, A.; Zhang, L.; Herzog, H.; Masedunskas, A.; Hardeman, E. C.; Gunning, P. W.; Del Monte-Nieto, G.; Harvey, R. P.; Samuel, M. S.; Pajic, M.; McGhee, E. J.; Johnsson, A. E.; Sansom, O. J.; Welch, H. C. E.; Morton, J. P.; Strathdee, D.; Anderson, K. I.; Timpson, P.
Responsible Garvan Author A/Prof Paul Timpson
Publisher Name Cell Reports
Published Date 2017-10-03
Published Volume 21
Published Issue 1
Published Pages 274-288
Status Published in-print
DOI 10.1016/j.celrep.2017.09.022
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/28978480