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Cell Rep. 2014 Mar 27;6(6):1153-1164. doi: 10.1016/j.celrep.2014.02.024. Epub 2014 Mar 13.

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

Author information

1
Signalling Programme, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
2
Beatson Institute for Cancer Research, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
3
Beatson Institute for Cancer Research, Switchback Road, Bearsden, Glasgow G61 1BD, UK; Garvan Institute of Medical Research and Kinghorn Cancer Centre, Cancer Research Program, St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, NSW, 2010 Sydney, Australia. Electronic address: p.timpson@garvan.org.au.
4
Signalling Programme, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK. Electronic address: heidi.welch@babraham.ac.uk.

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.

PMID:
24630994
PMCID:
PMC3988842
DOI:
10.1016/j.celrep.2014.02.024
[Indexed for MEDLINE]
Free PMC Article
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