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


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.

Type Journal
ISBN 2211-1247 (Electronic)
Authors Johnsson, A. K.; 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.; Welch, H. C.;
Publisher Name Cell Reports
Published Date 2014-03-01
Published Volume 6
Published Issue 6
Published Pages 1153-64
Status Published in-print
URL link to publisher's version! bmed/24630994
OpenAccess link to author's accepted manuscript version