The Rac-FRET mouse reveals tight spatiotemporal control of Rac activity in primary cells and tissues

Johnsson, A.-K. E. et al. (2014) The Rac-FRET mouse reveals tight spatiotemporal control of Rac activity in primary cells and tissues. Cell Reports, 6(6), pp. 1153-1164. (doi:10.1016/j.celrep.2014.02.024)

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Publisher's URL: http://dx.doi.org/10.1016/j.celrep.2014.02.024

Abstract

The small G protein family Rac has numerous regulators that integrate extracellular signals into tight spatiotemporal maps of its activity to promote specific cell morphologies and responses. Here, we have generated a mouse strain, Rac-FRET, which ubiquitously expresses the Raichu-Rac biosensor. It enables FRET imaging and quantification of Rac activity in live tissues and primary cells without affecting cell properties and responses. We assessed Rac activity in chemotaxing Rac-FRET neutrophils and found enrichment in leading-edge protrusions and unexpected longitudinal shifts and oscillations during protruding and stalling phases of migration. We monitored Rac activity in normal or disease states of intestinal, liver, mammary, pancreatic, and skin tissue, in response to stimulation or inhibition and upon genetic manipulation of upstream regulators, revealing unexpected insights into Rac signaling during disease development. The Rac-FRET strain is a resource that promises to fundamentally advance our understanding of Rac-dependent responses in primary cells and native environments.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Huels, Mr David and Kadir, Dr Shereen and Schwarz, Ms Juliana and Anderson, Professor Kurt and Timpson, Dr Paul and Nobis, Mr Max and McGhee, Dr Ewan and Morton, Dr Jennifer and Myant, Dr Kevin and Sansom, Professor Owen
Authors: Johnsson, A.-K. E., Dai, Y., Nobis, M., Baker, M. J., McGhee, E. J., Walker, S., Schwarz, J. P., Kadir, S., Morton, J. P., Myant, K. B., Huels, D. J., Segonds-Pichon, A., Sansom, O. J., Anderson, K. I., Timpson, P., and Welch, H. C.E.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cell Reports
Publisher:Elsevier
ISSN:2211-1247
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Cell Reports 6(6):1153-1164
Publisher Policy:Reproduced under a Creative Commons License

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