Transient Activations of Rac1 at the Lamellipodium Tip Trigger Membrane Protrusion

Mehidi, Amine; Rossier, Olivier; Schaks, Matthias; Chazeau, Anaël; Binamé, Fabien; Remorino, Amanda; Coppey, Mathieu; Karatas, Zeynep; Sibarita, Jean‐Baptiste; Rottner, Klemens; Moreau, Violaine; Giannone, Grégory

doi:10.1016/j.cub.2019.07.035

Cited by 39 publications

(31 citation statements)

References 71 publications

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“…IV. Immobilization of Rac at lamellipodial tips is mediated, at least in part, by WRC-binding [96]. Similar observations were previously made with the WAVE-related NPF N-WASP, reported to constitute a critical Arp2/3 complex activator in distinct subcellular structures.…”

Section: Regulation Of Wrc Localization Activity and Turnoversupporting

confidence: 77%

“…In fact, previously published work suggested interactions with both proteins and lipids to aid WRC accumulation at this site, e.g., with IRSp53, lamellipodin (Lpd) and the leading edge phospholipid phosphatidylinositol-3,4,5-trisphosphate [93–95]. Along these lines, recent single molecule tracking experiments of Rac at the lamellipodium tip confirmed surprisingly short residency times as compared to WRC, but they also revealed Rac immobilization to positively correlate with its activity state and effector binding, including WRC [96].…”

Section: Regulation Of Wrc Localization Activity and Turnovermentioning

confidence: 99%

“…In spite of aforementioned considerations, an alternative interpretation of existing data would be that Rac also contributes to localising WRC at the lamellipodium tip, last not least because constitutively active WRC lacking functional Rac binding sites shows strong impairment in lamellipodia induction and accumulation at their tips [77,80]. This conclusion is not necessarily incompatible with comparably transient residency times of Rac at lamellipodia tips [96]. Indeed, there is growing evidence that WRC accumulation and/or maintenance at protruding tips requires loose or transient interactions with lamellipodial building blocks, i.e.…”

Section: Regulation Of Wrc Localization Activity and Turnovermentioning

confidence: 99%

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Actin dynamics in cell migration

Schaks

Giannone

Rottner

2019

Essays in Biochemistry

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193

118

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Cell migration is an essential process, both in unicellular organisms such as amoeba and as individual or collective motility in highly developed multicellular organisms like mammals. It is controlled by a variety of activities combining protrusive and contractile forces, normally generated by actin filaments. Here, we summarize actin filament assembly and turnover processes, and how respective biochemical activities translate into different protrusion types engaged in migration. These actin-based plasma membrane protrusions include actin-related protein 2/3 complex-dependent structures such as lamellipodia and membrane ruffles, filopodia as well as plasma membrane blebs. We also address observed antagonisms between these protrusion types, and propose a model – also inspired by previous literature – in which a complex balance between specific Rho GTPase signaling pathways dictates the protrusion mechanism employed by cells. Furthermore, we revisit published work regarding the fascinating antagonism between Rac and Rho GTPases, and how this intricate signaling network can define cell behavior and modes of migration. Finally, we discuss how the assembly of actin filament networks can feed back onto their regulators, as exemplified for the lamellipodial factor WAVE regulatory complex, tightly controlling accumulation of this complex at specific subcellular locations as well as its turnover.

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Section: Regulation Of Wrc Localization Activity and Turnoversupporting

confidence: 77%

Section: Regulation Of Wrc Localization Activity and Turnovermentioning

confidence: 99%

Section: Regulation Of Wrc Localization Activity and Turnovermentioning

confidence: 99%

See 1 more Smart Citation

Actin dynamics in cell migration

Schaks

Giannone

Rottner

2019

Essays in Biochemistry

Self Cite

193

118

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“…SPT techniques unveiled the correlation between protein dynamics and protein activation and/or binding states. The recent application of SRM and SPT lead to a drastic rethinking of macromolecular assemblies including cadherin-based adhesions 21 , axons 22 , dendritic spines 23,24 , actin-based lamellipodium 25 and integrin-based focal adhesions (FAs) 26,27 .…”

Section: Introductionmentioning

confidence: 99%

Cell stretching is amplified by active actin remodelling to deform and recruit proteins in mechanosensitive structures

et al. 2020

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Detection and conversion of mechanical forces into biochemical signals control cell functions during physiological and pathological processes. Mechano-sensing is based on protein deformations and reorganizations, yet the molecular mechanisms in cells are still unclear. Using a cell stretching device compatible with super-resolution microscopy (SRM) and single protein tracking (SPT), we explored the nanoscale deformations and reorganizations of individual proteins inside mechano-sensitive structures. We achieved SRM after live stretching on intermediate filaments, microtubules and integrin adhesions. Simultaneous SPT and stretching showed that while integrins follow the elastic deformation of the substrate, actin filaments and talin also displayed lagged and transient inelastic responses associated with active acto-myosin remodeling and talin deformations. Capturing acute reorganizations of single-molecule during stretching showed that force-dependent vinculin recruitment is delayed and depends on the maturation state of integrin adhesions. Thus, cells respond to external forces by amplifying transiently and locally cytoskeleton displacements enabling protein deformation and recruitment in mechano-sensitive structures.

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“…In this case, the cells display impaired lamellipodia and utilize alternative filopodial protrusions. In addition, both Rac and Rho are active within the protruding lamellipodium, although the timing and localization of their activation differs during the protrusion cycle [ 4 , 5 , 82 , 83 , 84 ]. Thus, the protrusions can be driven by Rho and its effectors such as formins [ 82 , 85 ], or by the cooperation of formins and the Arp2/3 complex [ 86 ].…”

Section: Discussionmentioning

confidence: 99%

Quantitative Phase Imaging of Spreading Fibroblasts Identifies the Role of Focal Adhesion Kinase in the Stabilization of the Cell Rear

et al. 2020

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Cells attaching to the extracellular matrix spontaneously acquire front–rear polarity. This self-organization process comprises spatial activation of polarity signaling networks and the establishment of a protruding cell front and a non-protruding cell rear. Cell polarization also involves the reorganization of cell mass, notably the nucleus that is positioned at the cell rear. It remains unclear, however, how these processes are regulated. Here, using coherence-controlled holographic microscopy (CCHM) for non-invasive live-cell quantitative phase imaging (QPI), we examined the role of the focal adhesion kinase (FAK) and its interacting partner Rack1 in dry mass distribution in spreading Rat2 fibroblasts. We found that FAK-depleted cells adopt an elongated, bipolar phenotype with a high central body mass that gradually decreases toward the ends of the elongated processes. Further characterization of spreading cells showed that FAK-depleted cells are incapable of forming a stable rear; rather, they form two distally positioned protruding regions. Continuous protrusions at opposite sides results in an elongated cell shape. In contrast, Rack1-depleted cells are round and large with the cell mass sharply dropping from the nuclear area towards the basal side. We propose that FAK and Rack1 act differently yet coordinately to establish front–rear polarity in spreading cells.

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Transient Activations of Rac1 at the Lamellipodium Tip Trigger Membrane Protrusion

Cited by 39 publications

References 71 publications

Actin dynamics in cell migration

Actin dynamics in cell migration

Cell stretching is amplified by active actin remodelling to deform and recruit proteins in mechanosensitive structures

Quantitative Phase Imaging of Spreading Fibroblasts Identifies the Role of Focal Adhesion Kinase in the Stabilization of the Cell Rear

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