Protein kinase A governs a RhoA-RhoGDI protrusion-retraction pacemaker in migrating cells

Tkachenko, E. and Sabouri-Ghomi, M. and Pertz, O. and Kim, C. and Gutierrez, E. and Machacek, M. and Groisman, A. and Danuser, G. and Ginsberg, M. H.. (2011) Protein kinase A governs a RhoA-RhoGDI protrusion-retraction pacemaker in migrating cells. Nature cell biology, Vol. 13, H. 6. pp. 660-667.

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Official URL: http://edoc.unibas.ch/dok/A6004788

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Cell Migration and Neuritogenesis (Pertz)
UniBasel Contributors:Pertz, Olivier
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 May 2015 08:45
Deposited On:27 Feb 2014 15:45

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