Gradients Of Rac1 Nanoclusters Support Spatial Patterns of Rac1 Signaling

Remorino, Amanda; Beco, Simon de; Cayrac, Fanny; Federico, Fahima Di; Cornilleau, Gaetan; Gautreau, Alexis; Parrini, Maria Carla; Masson, Jean-Baptiste; Dahan, Maxime; Coppey, Mathieu

doi:10.2139/ssrn.3155604

Cited by 12 publications

(19 citation statements)

References 30 publications

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“…The signaling mechanisms leading to the reduction in MPA density prior to protrusion may not be identical between cell types, as RhoGTPases and their effectors, capping and severing proteins, as well as Arp2/3 and formins, are known to have context-dependent roles in migration (37). Beyond the control of cell motility, the interface between membrane and cortex plays vital roles in exocytosis (39), generation of ER-PM junctions (40), diffusionreaction dynamics kinetics at the membrane (5,41), and mechanotransduction (42). MPA density changes likely control specific steps in these processes and future studies are needed to explore the role of local MPA density in controlling other membrane localized processes regulated by cortical actin.…”

Section: Discussionmentioning

confidence: 99%

Membrane-proximal F-actin restricts local membrane protrusions and directs cell migration

Bisaria

Hayer

Garbett

et al. 2020

Science

119

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Cell migration is driven by local membrane protrusion through directed polymerization of F-actin at the front. However, F-actin next to the plasma membrane also tethers the membrane and thus resists outgoing protrusions. Here, we developed a fluorescent reporter to monitor changes in the density of membrane-proximal F-actin (MPA) during membrane protrusion and cell migration. Unlike the total F-actin concentration, which was high in the front of migrating cells, MPA density was low in the front and high in the back. Back-to-front MPA density gradients were controlled by higher cofilin-mediated turnover of F-actin in the front. Furthermore, nascent membrane protrusions selectively extended outward from areas where MPA density was reduced. Thus, locally low MPA density directs local membrane protrusions and stabilizes cell polarization during cell migration.

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Section: Discussionmentioning

confidence: 99%

Membrane-proximal F-actin restricts local membrane protrusions and directs cell migration

Bisaria

Hayer

Garbett

et al. 2020

Science

119

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“…It is likely that balance in the activity of GEFs and GAPs at the front of moving cells is important for turnover of protrusions and adhesions to drive polarized migration. [16][17][18][19][20] Moreover, spatial separation of GEFs and GAPs may be required for precise regulation of Rac activity to form a single polarized protrusion. 17 How Rac GEFs and GAPs spatiotemporally collaborate to ensure front-rear polarization and efficient migration should be explored in future studies.…”

Section: Discussionmentioning

confidence: 99%

“…[13][14][15] At the front of polarized cells, Rac1 activity is spatiotemporally regulated by GEFs and GAPs, and continuous GTP/GDP cycling through these proteins is thought to be necessary for turnover of protrusions and adhesions to drive efficient migration. [16][17][18] Indeed, highly or constitutively activated Rac1 in cells leads to loss of cell polarity and inhibition of directed migration. 19,20 Therefore, precise regulation of Rac activity by GEFs and GAPs should be required for effective motility with front-rear cell axis.…”

mentioning

confidence: 99%

FilGAP, a GAP protein for Rac, regulates front‐rear polarity and tumor cell migration through the ECM

et al. 2021

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Malignant tumor cells acquire abnormal motility and invade through various extracellular matrix (ECM) components with distinct composition and architecture, including basement membrane and interstitial collagen networks, and leave a blood or lymphatic vessel and invade the surrounding tissue parenchyma. 1,2 Actin cytoskeletal dynamics is essential for cell polarization and migration. 3-6 Migrating cells are characterized by a sustained front-rear asymmetry, with a front enriched in filamentous actin (F-actin) and a rear made of actomyosin filaments. Rho small GTPase (Rho GTPase) Rac1 induces membrane protrusion at the front of migrating cells through actin polymerization, whereas the activity of another Rho GTPase RhoA is required for tail retraction at the rear through activation of actomyosin contraction. 3,7-10 This acquisition of front-rear polarity is important for effective motility of various cell types including tumor cells.

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“…For example, Ras/Rho signaling is intimately linked with membrane lipids in all eukaryotes. Interaction with anionic lipids is important for their plasma membrane targeting (3,4), but also mediates the clustering of these small GTPases at the cell surface into nanometer scale membrane domains (5)(6)(7)(8). In particular, the phospholipid phosphatidylserine is involved in the nanoclustering and signaling of some GTPase, such as K-Ras in human and Cdc42 in yeast (2,7,8).…”

Section: Main Textmentioning

confidence: 99%

Developmental control of plant Rho GTPase nano-organization by the lipid phosphatidylserine

Platre

Bayle

Armengot

et al. 2019

Science

192

233

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Rho guanosine triphosphatases (GTPases) are master regulators of cell signaling, but how they are regulated depending on the cellular context is unclear. We found that the phospholipid phosphatidylserine acts as a developmentally controlled lipid rheostat that tunes Rho GTPase signaling in Arabidopsis. Live superresolution single-molecule imaging revealed that the protein Rho of Plants 6 (ROP6) is stabilized by phosphatidylserine into plasma membrane nanodomains, which are required for auxin signaling. Our experiments also revealed that the plasma membrane phosphatidylserine content varies during plant root development and that the level of phosphatidylserine modulates the quantity of ROP6 nanoclusters induced by auxin and hence downstream signaling, including regulation of endocytosis and gravitropism. Our work shows that variations in phosphatidylserine levels are a physiological process that may be leveraged to regulate small GTPase signaling during development.

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Gradients Of Rac1 Nanoclusters Support Spatial Patterns of Rac1 Signaling

Cited by 12 publications

References 30 publications

Membrane-proximal F-actin restricts local membrane protrusions and directs cell migration

Membrane-proximal F-actin restricts local membrane protrusions and directs cell migration

FilGAP, a GAP protein for Rac, regulates front‐rear polarity and tumor cell migration through the ECM

Developmental control of plant Rho GTPase nano-organization by the lipid phosphatidylserine

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