Nature. 2006 Apr 20;440(7087):1069-72. Epub 2006 Mar 19.
Spatiotemporal dynamics of RhoA activity in migrating cells.
Pertz O, Hodgson L, Klemke RL, Hahn KM.
[1] University of North Carolina at Chapel Hill, Department of Pharmacology and
Lineberger Cancer Center, Chapel Hill, North Carolina 27599, USA [2] Department
of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road,
La Jolla, California 92037, USA [3] daggerPresent addresses: University of
California at San Diego, Department of Pathology and Moores Cancer Center, Basic
Science Building, Room 1040, 9500 Gilman Drive, MC 0612, La Jolla, California
92093, USA (O.P., R.L.K.); University of North Carolina at Chapel Hill,
Department of Pharmacology and Lineberger Cancer Center, Chapel Hill, North
Carolina 27599, USA (L.H., K.M.H.).
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 body. However,
there is evidence that RhoA also regulates membrane protrusion. 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 activity. Our data therefore show that different
extracellular cues induce distinct patterns of RhoA signalling during membrane
protrusion.
PMID: 16547516 [PubMed - as supplied by publisher]
