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...

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Podrobná bibliografie
Vydáno v:	Cell reports (Cambridge) Ročník 6; číslo 6; s. 1153 - 1164
Hlavní autoři:	Johnsson, Anna-Karin E., Dai, Yanfeng, Nobis, Max, Baker, Martin J., McGhee, Ewan J., Walker, Simon, Schwarz, Juliane P., Kadir, Shereen, Morton, Jennifer P., Myant, Kevin B., Huels, David J., Segonds-Pichon, Anne, Sansom, Owen J., Anderson, Kurt I., Timpson, Paul, Welch, Heidi C.E.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Cell Press 01.03.2014 Elsevier
Témata:	Animals Enzyme Activation Fluorescence Resonance Energy Transfer - methods Mice Neutrophils - cytology Neutrophils - enzymology rac GTP-Binding Proteins - chemistry rac GTP-Binding Proteins - metabolism Resource Signal Transduction Spatio-Temporal Analysis
ISSN:	2211-1247, 2211-1247
On-line přístup:	Získat plný text
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Popis
Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: Research Centre for Animal Genetic Resources of the Mongolia Plateau, Inner Mongolia University, 235 West University Road, 010021 Hohhot, China These authors contributed equally to this work
ISSN:	2211-1247 2211-1247
DOI:	10.1016/j.celrep.2014.02.024