Membrane Flow Drives an Adhesion-Independent Amoeboid Cell Migration Mode

O’Neill, Patrick; Castillo‐Badillo, Jean A.; Meshik, Xenia; Kalyanaraman, Vani; Melgarejo, Krystal; Gautam, N.

doi:10.1016/j.devcel.2018.05.029

Cited by 124 publications

(183 citation statements)

References 73 publications

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“…According to the Glideosome model, the force generated for motility and invasion relies exclusively on F‐actin polymerised at the apical tip of the parasite by the action of Formin‐1 and translocated within the narrow space (~30 nm) between the IMC and PM of the parasite . However, recent studies suggest that the parasite can also use other motility systems, such as a secretory‐endocytic cycle that produces retrograde membrane flow , similar to the fountain flow model suggested for other eukaryotes .…”

Section: Introductionmentioning

confidence: 96%

Apicomplexan F‐actin is required for efficient nuclear entry during host cell invasion

et al. 2019

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The obligate intracellular parasites Toxoplasma gondii and Plasmodium spp. invade host cells by injecting a protein complex into the membrane of the targeted cell that bridges the two cells through the assembly of a ring‐like junction. This circular junction stretches while the parasites apply a traction force to pass through, a step that typically concurs with transient constriction of the parasite body. Here we analyse F‐actin dynamics during host cell invasion. Super‐resolution microscopy and real‐time imaging highlighted an F‐actin pool at the apex of pre‐invading parasite, an F‐actin ring at the junction area during invasion but also networks of perinuclear and posteriorly localised F‐actin. Mutant parasites with dysfunctional acto‐myosin showed significant decrease of junctional and perinuclear F‐actin and are coincidently affected in nuclear passage through the junction. We propose that the F‐actin machinery eases nuclear passage by stabilising the junction and pushing the nucleus through the constriction. Our analysis suggests that the junction opposes resistance to the passage of the parasite's nucleus and provides the first evidence for a dual contribution of actin‐forces during host cell invasion by apicomplexan parasites.

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Section: Introductionmentioning

confidence: 96%

Apicomplexan F‐actin is required for efficient nuclear entry during host cell invasion

et al. 2019

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“…For tumoral cells, one theoretical model of blebbing mentioned the possibility of migration in suspension by shape changes 16 , whereas other modeling efforts validated a swimming mechanism based on shape deformation for the case of cyanobacteria 17 and microalgae 2 . A recent study on mesenchymatous macrophages cell line RAW 264.7 reported an amoeboid swimming mode artificially triggered by optogentic activation of actomyosin contractility in cell rear 18 . Propulsion convincingly involved membrane treadmilling, whereas contribution deformations was not assessed.…”

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confidence: 99%

Mammalian Amoeboid Swimming is propelled by molecular and not protrusion-based paddling in Lymphocytes

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Farutin

et al. 2019

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Mammalian cells developed two main migration modes. The slow mesenchymatous mode, like fibroblasts crawling, relies on maturation of adhesion complexes and actin fiber traction, while the fast amoeboid mode, observed exclusively for leukocytes and cancer cells, is characterized by weak adhesion, highly dynamic cell shapes, and ubiquitous motility on 2D and in 3D solid matrix. In both cases, interactions with the substrate by adhesion or friction are widely accepted as a prerequisite for mammalian cell motility, which precludes swimming. We show here experimentally and computationally that leukocytes do swim, and that propulsion is not fueled by waves of cell deformation but by a rearward and inhomogeneous treadmilling of the cell envelope. We model the propulsion as a molecular paddling by transmembrane proteins linked to and advected by the actin cortex, whereas freely diffusing transmembrane proteins hinder swimming. This mechanism explains that swimming is five times slower than the cortex retrograde flow. Resultantly the ubiquitous ability of mammalian amoeboid cells to migrate in various environments can be explained for lymphocytes by a single machinery of envelope treadmilling.

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“…Since the stable bleb-driven morphology was adhesion deficient, we tried to find how these cells move. It has been shown previously that adhesion-independent amoeboid migration is driven by a rearward flow of plasma membrane (O'Neill et al, 2018). When the unpolarized cells were stained with plans membrane stain CellMask Orange (CMO), most of the fluorescence was observed on the membrane and internal vesicles ( Fig.…”

Section: Temporal Progression Of Morphological and Motility Changes Dmentioning

confidence: 85%

Polarized Entamoeba: A model for stable bleb driven motility

Krishnan

Ghosh

2019

Preprint

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statementPentoxifylline, the adenosine receptor antagonist induced a stable bleb driven polarized morphology in Entamoeba characterized by fast, directionally persistent and highly chemotactic motility. AbstractProtozoan parasites Entamoeba histolytica and Entamoeba invadens formed a polarized phenotype, an elongated shape with a single leading edge and a trailing edge when treated with pentoxifylline. The leading edge of the polarized morphology was a spherical protrusion devoid of F-actin but with occasional F-actin scars, indicating the presence of bleb. The polarized form was stable bleb driven since the blebbing was limited to the leading edge. Pentoxifylline induced chemokinesis in Entamoeba as it switched the motility pattern from slow and random to fast and directionally persistent. Pentoxifylline speeded up the cell aggregation in E. invadens during growth and encystation due to enhanced chemotaxis of the polarized form. The transformation of non-polarized adherent trophozoites to nonadherent stable bleb driven form occurred via lamellipodial and bleb driven adherent intermediate phenotypes. The nonadherent polarized phenotype was highly motile under confinement and moved by rearward plasma membrane flow.In contrast to pentoxifylline, adenosine, the adenosine receptor agonist, stimulated the formation of multiple protrusions leading to random motility. Thus pentoxifylline might prevent lateral protrusions by inhibiting adenosine receptor, producing the monopodial polarized morphology.Cell migration is an important event in embryonic development, wound healing, immune response, and cancer progression. The first step in cell migration is the polarization during which the cells break symmetry to form a leading edge and a trailing edge. Depending on the leading edge, motility can be of two types, lamellipodial motility driven by actin polymerization and pressure driven blebbing. Cells like keratocytes and fibroblasts use lamellipodia at the leading edge while primordial germ cells and amoeboid tumor cells use blebbing motility (Blaser et al., 2006;Paňková et al., 2010). Bleb driven cell migration have been reported in many biological events like embryonic development, Dictyostelium chemotaxis, and cancer metastasis (Fackler and Grosse, 2008) but unlike lamellipodial motility, its mechanics is not well understood.Enteric parasite Entamoeba histolytica is a highly motile organism, and it has been reported to use only the bleb driven motility both in vitro and in vivo and thus can be considered as an important model to study blebbing (Maugis et al., 2010). As shown previously in progenitor cells (Diz-Muñoz et al., 2010), blebbing reduced directional persistence in E.histolytica. Here we report that both human pathogen E. histolytica and its reptilian counterpart and encystation model Entamoeba invadens readily formed a fast moving, elongated morphology when treated with a millimolar concentration of methylxanthines like pentoxifylline or caffeine.This morphology showed a single leading edge with stable bleb, ma...

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Membrane Flow Drives an Adhesion-Independent Amoeboid Cell Migration Mode

Cited by 124 publications

References 73 publications

Apicomplexan F‐actin is required for efficient nuclear entry during host cell invasion

Apicomplexan F‐actin is required for efficient nuclear entry during host cell invasion

Mammalian Amoeboid Swimming is propelled by molecular and not protrusion-based paddling in Lymphocytes

Polarized Entamoeba: A model for stable bleb driven motility

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