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

Nobis, M. et al. (2017) A RhoA-FRET biosensor mouse for intravital imaging in normal tissue homeostasis and disease contexts. Cell Reports, 21, pp. 274-288. (doi: 10.1016/j.celrep.2017.09.022) (PMID:28978480)

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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.

Item Type:Articles
Additional Information:P.T., M.N., D.H., S.C.W., M.K., M.C.L., W.L., N.R., C.V., J.R.W.C., and A. Magenau were funded by NHMRC project grants (1043501, 1089497, 1105640, and 1129401), ARC Future (FT120100880) and Len Ainsworth Pancreatic Cancer Fellowships, the Cancer Council NSW (RG 14-08), Sydney Catalyst, and Tour de Cure. K.I.A., M.N., E.J.M., A. Mrowinska, S.K., J.P.S., D. Strathdee, D. Stevenson, O.J.S., and J.P.M. were funded by a CRUK core grant.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Schwarz, Ms Juliana and McGhee, Dr Ewan and Kadir, Dr Shereen and Strathdee, Dr Douglas and Timpson, Dr Paul and Morton, Professor Jen and Stevenson, Dr David and Sansom, Professor Owen
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., Mrwowinksa, 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.-K. E., Sansom, O. J., Welch, H. C.E., Morton, J. P., Strathdee, D., Anderson, K. I., and Timpson, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cell Reports
Publisher:Elsevier
ISSN:2211-1247
ISSN (Online):2211-1247
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Cell Reports 21:274-288
Publisher Policy:Reproduced under a Creative Commons license

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