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

Eugene Tkachenko, Mohsen Sabouri-Ghomi, Olivier Pertz, Chungho Kim, Edgar Gutierrez, Matthias MacHacek, Alex Groisman, Gaudenz Danuser, Mark H. Ginsberg

Research output: Contribution to journalArticle

96 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)660-668
Number of pages9
JournalNature Cell Biology
Volume13
Issue number6
DOIs
Publication statusPublished - 2011 Jun 1
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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    Tkachenko, E., Sabouri-Ghomi, M., Pertz, O., Kim, C., Gutierrez, E., MacHacek, M., Groisman, A., Danuser, G., & Ginsberg, M. H. (2011). Protein kinase A governs a RhoA-RhoGDI protrusion-retraction pacemaker in migrating cells. Nature Cell Biology, 13(6), 660-668. https://doi.org/10.1038/ncb2231