Abstract：
:The cyclical protrusion and retraction of the leading edge is a hallmark of many migrating cells involved in processes such as development, inflammation and tumorigenesis. The molecular identity of the signalling mechanisms that control these cycles has remained unknown. Here, we used live-cell imaging of biosensors to monitor spontaneous morphodynamic and signalling activities, and employed correlative image analysis to examine the role of cyclic-AMP-activated protein kinase A (PKA) in protrusion regulation. PKA activity at the leading edge is closely synchronized with rapid protrusion and with the activity of RhoA. Ensuing PKA phosphorylation of RhoA and the resulting increased interaction between RhoA and RhoGDI (Rho GDP-dissociation inhibitor) establish a negative feedback mechanism that controls the cycling of RhoA activity at the leading edge. Thus, cooperation between PKA, RhoA and RhoGDI forms a pacemaker that governs the morphodynamic behaviour of migrating cells.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Tkachenko E,Sabouri-Ghomi M,Pertz O,Kim C,Gutierrez E,Machacek M,Groisman A,Danuser G,Ginsberg MHdoi
10.1038/ncb2231subject
Has Abstractpub_date
2011-06-01 00:00:00pages
660-7issue
6eissn
1465-7392issn
1476-4679pii
ncb2231journal_volume
13pub_type
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