Spatio-temporal co-ordination of RhoA, Rac1 and Cdc42 activation during prototypical edge protrusion and retraction dynamics

Martin, Katrin; Reimann, Andreas; Fritz, Rafael D; Ryu, Hyunryul; Jeon, Noo Li; Pertz, Olivier (2016). Spatio-temporal co-ordination of RhoA, Rac1 and Cdc42 activation during prototypical edge protrusion and retraction dynamics. Scientific Reports, 6, p. 21901. Nature Publishing Group 10.1038/srep21901

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The three canonical Rho GTPases RhoA, Rac1 and Cdc42 co-ordinate cytoskeletal dynamics. Recent studies indicate that all three Rho GTPases are activated at the leading edge of motile fibroblasts, where their activity fluctuates at subminute time and micrometer length scales. Here, we use a microfluidic chip to acutely manipulate fibroblast edge dynamics by applying pulses of platelet-derived growth factor (PDGF) or the Rho kinase inhibitor Y-27632 (which lowers contractility). This induces acute and robust membrane protrusion and retraction events, that exhibit stereotyped cytoskeletal dynamics, allowing us to fairly compare specific morphodynamic states across experiments. Using a novel Cdc42, as well as previously described, second generation RhoA and Rac1 biosensors, we observe distinct spatio-temporal signaling programs that involve all three Rho GTPases, during protrusion/retraction edge dynamics. Our results suggest that Rac1, Cdc42 and RhoA regulate different cytoskeletal and adhesion processes to fine tune the highly plastic edge protrusion/retraction dynamics that power cell motility.

Item Type:

Journal Article (Original Article)

Division/Institute:

09 Interdisciplinary Units > Microscopy Imaging Center (MIC)
08 Faculty of Science > Department of Biology > Institute of Cell Biology

UniBE Contributor:

Pertz, Olivier

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

2045-2322

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Olivier Pertz

Date Deposited:

03 May 2016 09:38

Last Modified:

27 Feb 2020 18:06

Publisher DOI:

10.1038/srep21901

PubMed ID:

26912264

BORIS DOI:

10.7892/boris.81849

URI:

https://boris.unibe.ch/id/eprint/81849

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