TY - JOUR
T1 - Spatiotemporal dynamics of RhoA activity in migrating cells
AU - Pertz, Olivier
AU - Hodgson, Louis
AU - Klemke, Richard L.
AU - Hahn, Klaus M.
N1 - Funding Information:
Acknowledgements We are grateful to G. Bokoch, P. Sun, M. Schwartz, R. Tsien, C. Der and E. Sahai for reagents, and to F. Shen for help with image analysis. This work was supported by grants from the Swiss National Science Foundation, Roche Research Foundation, Novartis and Philip Morris to O.P., and from the National Institutes of Health to K.M.H. and R.L.K.
PY - 2006/4/20
Y1 - 2006/4/20
N2 - Rho family GTPases regulate the actin and adhesion dynamics that control cell migration. Current models postulate that Rac promotes membrane protrusion at the leading edge and that RhoA regulates contractility in the cell body1,2. However, there is evidence that RhoA also regulates membrane protrusion3,4. Here we use a fluorescent biosensor, based on a novel design preserving reversible membrane interactions, to visualize the spatiotemporal dynamics of RhoA activity during cell migration. In randomly migrating cells, RhoA activity is concentrated in a sharp band directly at the edge of protrusions. It is observed sporadically in retracting tails, and is low in the cell body. RhoA activity is also associated with peripheral ruffles and pinocytic vesicles, but not with dorsal ruffles induced by platelet-derived growth factor (PDGF). In contrast to randomly migrating cells, PDGF-induced membrane protrusions have low RhoA activity, potentially because PDGF strongly activates Rac, which has previously been shown to antagonize RhoA activity5,6. Our data therefore show that different extracellular cues induce distinct patterns of RhoA signalling during membrane protrusion.
AB - Rho family GTPases regulate the actin and adhesion dynamics that control cell migration. Current models postulate that Rac promotes membrane protrusion at the leading edge and that RhoA regulates contractility in the cell body1,2. However, there is evidence that RhoA also regulates membrane protrusion3,4. Here we use a fluorescent biosensor, based on a novel design preserving reversible membrane interactions, to visualize the spatiotemporal dynamics of RhoA activity during cell migration. In randomly migrating cells, RhoA activity is concentrated in a sharp band directly at the edge of protrusions. It is observed sporadically in retracting tails, and is low in the cell body. RhoA activity is also associated with peripheral ruffles and pinocytic vesicles, but not with dorsal ruffles induced by platelet-derived growth factor (PDGF). In contrast to randomly migrating cells, PDGF-induced membrane protrusions have low RhoA activity, potentially because PDGF strongly activates Rac, which has previously been shown to antagonize RhoA activity5,6. Our data therefore show that different extracellular cues induce distinct patterns of RhoA signalling during membrane protrusion.
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U2 - 10.1038/nature04665
DO - 10.1038/nature04665
M3 - Article
C2 - 16547516
AN - SCOPUS:33646197411
SN - 0028-0836
VL - 440
SP - 1069
EP - 1072
JO - Nature
JF - Nature
IS - 7087
ER -