Optogenetic dissection of Rac1 and Cdc42 gradient shaping

Beco, Simon de; Vaidžiulytė, Kotryna; Manzi, John; Dalier, Fabrice; Federico, Fahima Di; Cornilleau, Gaetan; Dahan, Maxime; Coppey, Mathieu

doi:10.1038/s41467-018-07286-8

Cited by 72 publications

(77 citation statements)

References 71 publications

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“…This difference leads to marked changes in the cellular distribution of RhoA-ROCK versus RhoA-DIA effector complexes ( Figure 1A and B ). Differential localization of DIA and ROCK, as well as different spatial distribution of GEFs, GAPs, and guanosine nucleotide dissociation inhibitors ( de Beco et al, 2018 ; Nikonova et al, 2013 ; Tsyganov et al, 2012 ), generate distinct circuitries of RhoA-Rac1 interactions and different RhoA and Rac1 kinetics along a cell ( Figure 2B–F ). Oscillations of RhoA and Rac1 activities at the leading edge guide protrusions and retractions, whereas high, stable RhoA activity and low Rac1-GTP at the rear maintain focal adhesions and the cell attachment to the substrate.…”

Section: Discussionmentioning

confidence: 99%

Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration

Bolado-Carrancio

Rukhlenko

Nikonova

et al. 2020

eLife

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Migrating cells need to coordinate distinct leading and trailing edge dynamics but the underlying mechanisms are unclear. Here, we combine experiments and mathematical modeling to elaborate the minimal autonomous biochemical machinery necessary and sufficient for this dynamic coordination and cell movement. RhoA activates Rac1 via DIA and inhibits Rac1 via ROCK, while Rac1 inhibits RhoA through PAK. Our data suggest that in motile, polarized cells, RhoA–ROCK interactions prevail at the rear, whereas RhoA-DIA interactions dominate at the front where Rac1/Rho oscillations drive protrusions and retractions. At the rear, high RhoA and low Rac1 activities are maintained until a wave of oscillatory GTPase activities from the cell front reaches the rear, inducing transient GTPase oscillations and RhoA activity spikes. After the rear retracts, the initial GTPase pattern resumes. Our findings show how periodic, propagating GTPase waves coordinate distinct GTPase patterns at the leading and trailing edge dynamics in moving cells.

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Section: Discussionmentioning

confidence: 99%

Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration

Bolado-Carrancio

Rukhlenko

Nikonova

et al. 2020

eLife

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show abstract

“…1A and 1B). Differential localization of DIA and ROCK (as well as different spatial distribution of GEFs, GAPs, and guanosine nucleotide dissociation inhibitors (de Beco et al, 2018;Nikonova et al, 2013;Tsyganov et al, 2012)) can generate distinct circuitries of RhoA-Rac1 interactions and different RhoA and Rac1 kinetics along a cell ( Fig. 2B-F).…”

Section: Discussionmentioning

confidence: 99%

Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration

Bolado-Carrancio

Rukhlenko

Nikonova

et al. 2020

Preprint

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Migrating cells need to coordinate distinct leading and trailing edge dynamics but the underlying mechanisms are unclear. Here, we combine experiments and mathematical modeling to elaborate the minimal autonomous biochemical machinery necessary and sufficient for this dynamic coordination and cell movement. RhoA activates Rac1 via DIA and inhibits Rac1 via ROCK, while Rac1 inhibits RhoA through PAK. Our data suggest that in motile, polarized cells, RhoA-ROCK interactions prevail at the rear whereas RhoA-DIA interactions dominate at the front where Rac1/Rho oscillations drive protrusions and retractions. At the rear, high RhoA and low Rac1 activities are maintained until a wave of oscillatory GTPase activities from the cell front reaches the rear, inducing transient GTPase oscillations and RhoA activity spikes. After the rear retracts, the initial GTPase pattern resumes. Our findings show how periodic, propagating GTPase waves coordinate distinct GTPase patterns at the leading and trailing edge dynamics in moving cells.

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“…An excellent approach is the use of optogenetics to reversibly trigger signaling with spatial and temporal control in the subsecond range [176,177]. Such light-sensitive tools have already been successfully developed to control the activity of endogenous Rho GTPases in various settings [178][179][180] and can easily be combined with genetically encoded biosensors for monitoring local Rho GTPase or RhoGEF activity [47,62,64].…”

Section: Discussionmentioning

confidence: 99%

Spatiotemporal Control of Intracellular Membrane Trafficking by Rho GTPases

Noll

Haußer

2019

Cells

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As membrane-associated master regulators of cytoskeletal remodeling, Rho GTPases coordinate a wide range of biological processes such as cell adhesion, motility, and polarity. In the last years, Rho GTPases have also been recognized to control intracellular membrane sorting and trafficking steps directly; however, how Rho GTPase signaling is regulated at endomembranes is still poorly understood. In this review, we will specifically address the local Rho GTPase pools coordinating intracellular membrane trafficking with a focus on the endo-and exocytic pathways. We will further highlight the spatiotemporal molecular regulation of Rho signaling at endomembrane sites through Rho regulatory proteins, the GEFs and GAPs. Finally, we will discuss the contribution of dysregulated Rho signaling emanating from endomembranes to the development and progression of cancer.an inactive GDP-bound and an active GTP-bound state. Rho GDP/GTP cycling is tightly regulated by guanine nucleotide exchange factors (GEFs) that promote the formation of the active GTP-bound form through exchanging GDP for GTP. On the contrary, GTPase-activating proteins (GAPs) catalyze the intrinsic GTPase activity and promote the formation of inactive GDP-bound Rho. This inactive state can be subsequently recognized by guanine nucleotide dissociation inhibitors (GDIs), which sequester Rho GTPases in the cytosol [5,6] (Figure 1). Whereas classical Rho GTPases are regulated by GDP/GTP cycling, atypical Rho GTPases are regulated by other mechanisms that occur in particular at the transcriptional and post-translational level [7]. In the case of atypical Rho GTPases, GTP is usually constitutively bound, either because these Rho GTPases possess high intrinsic nucleotide exchange activity or have substitutions in their GTPase domain that prevent GTP hydrolysis.

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Optogenetic dissection of Rac1 and Cdc42 gradient shaping

Cited by 72 publications

References 71 publications

Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration

Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration

Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration

Spatiotemporal Control of Intracellular Membrane Trafficking by Rho GTPases

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