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Gradients Of Rac1 Nanoclusters Support Spatial Patterns of Rac1 Signaling

65 Pages Posted: 6 Apr 2018 Sneak Peek Status: Published

See all articles by Amanda Remorino

Amanda Remorino

Université Paris VI Pierre et Marie Curie - Laboratory Physico-Chemistry

Simon De Beco

Université Paris VI Pierre et Marie Curie - Laboratory Physico-Chemistry

Fanny Cayrac

Université Paris VI Pierre et Marie Curie - Laboratory Physico-Chemistry

Fahima Di Federico

Université Paris VI Pierre et Marie Curie - Laboratory Physico-Chemistry

Gaetan Cornilleau

Université Paris VI Pierre et Marie Curie - Laboratory Physico-Chemistry; PSL Research University - Institut Curie

Alexis Gautreau

University of Paris-Saclay - Ecole Polytechnique

Maria Carla Parrini

Université Paris VI Pierre et Marie Curie - Research Center

Jean-Baptiste Masson

University of Paris-Saclay - Decision and Bayesian Computation; University of Paris-Saclay - Center of Bioinformatics, BioStatistics and Integrative Biology

Maxime Dahan

Université Paris VI Pierre et Marie Curie - Laboratory Physico-Chemistry

Mathieu Coppey

Université Paris VI Pierre et Marie Curie - Laboratory Physico-Chemistry

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Abstract

The dynamics of the cytoskeleton and cell shape relies on the coordinated activation of RhoGTPase molecular switches. Among them, Rac1 participates to the orchestration in space and time of actin branching and protrusion/retraction cycles of the lamellipodia at the cell front during mesenchymal migration. Biosensor imaging has revealed a graded concentration of active GTP-loaded Rac1 in protruding regions of the cell. Here, using single molecule imaging and super-resolution microscopy, we reveal an additional supramolecular organization of Rac1. We find that, similarly to H-Ras, Rac1 partitions and is immobilized into nanoclusters of 50-100 molecules each. These nanoclusters assemble due to the interaction of the polybasic tail of Rac1 with the phosphoinositide lipids PIP2 and PIP3. The additional interactions with GEFs, GAPs, downstream effectors, and possibly other partners are responsible for an enrichment of Rac1 nanoclusters in protruding regions of the cell. Using optogenetics and micropatterning tools, we find that activation of Rac1 leads to its immobilization in nanoclusters and that the local level of Rac1 activity matches the local density of nanoclusters. Altogether, our results show that subcellular patterns of Rac1 activity are supported by gradients of signaling nanodomains of heterogeneous molecular composition, which presumably act as discrete signaling platforms. This finding implies that graded distributions of nanoclusters might encode spatial information.

Suggested Citation

Remorino, Amanda and De Beco, Simon and Cayrac, Fanny and Di Federico, Fahima and Cornilleau, Gaetan and Gautreau, Alexis and Parrini, Maria Carla and Masson, Jean-Baptiste and Dahan, Maxime and Coppey, Mathieu, Gradients Of Rac1 Nanoclusters Support Spatial Patterns of Rac1 Signaling (2018). Available at SSRN: https://ssrn.com/abstract=3155604 or http://dx.doi.org/10.2139/ssrn.3155604
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Amanda Remorino

Université Paris VI Pierre et Marie Curie - Laboratory Physico-Chemistry

175 Rue du Chevaleret
Paris, 75013
France

Simon De Beco

Université Paris VI Pierre et Marie Curie - Laboratory Physico-Chemistry

175 Rue du Chevaleret
Paris, 75013
France

Fanny Cayrac

Université Paris VI Pierre et Marie Curie - Laboratory Physico-Chemistry

175 Rue du Chevaleret
Paris, 75013
France

Fahima Di Federico

Université Paris VI Pierre et Marie Curie - Laboratory Physico-Chemistry

175 Rue du Chevaleret
Paris, 75013
France

Gaetan Cornilleau

Université Paris VI Pierre et Marie Curie - Laboratory Physico-Chemistry

175 Rue du Chevaleret
Paris, 75013
France

PSL Research University - Institut Curie

26 rue d'Ulm
Paris cedex 05
Paris, 75248
France

Alexis Gautreau

University of Paris-Saclay - Ecole Polytechnique

55 Avenue de Paris
Versailles, 78000
France

Maria Carla Parrini

Université Paris VI Pierre et Marie Curie - Research Center ( email )

175 Rue du Chevaleret
Paris, 75013
France

Jean-Baptiste Masson

University of Paris-Saclay - Decision and Bayesian Computation

75724 Paris CEDEX 15
France

University of Paris-Saclay - Center of Bioinformatics, BioStatistics and Integrative Biology

75724 Paris CEDEX 15
France

Maxime Dahan

Université Paris VI Pierre et Marie Curie - Laboratory Physico-Chemistry

175 Rue du Chevaleret
Paris, 75013
France

Mathieu Coppey (Contact Author)

Université Paris VI Pierre et Marie Curie - Laboratory Physico-Chemistry ( email )

175 Rue du Chevaleret
Paris, 75013
France

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