Steering cell migration: lamellipodium dynamics and the regulation of directional persistence

Krause, Matthias; Gautreau, Alexis

doi:10.1038/nrm3861

Cited by 524 publications

(557 citation statements)

References 206 publications

Supporting

Mentioning

540

Contrasting

Order By: Relevance

“…actin | Ena/VASP | TIRF | cluster | formin T he highly coordinated spatial and temporal control of the assembly and disassembly of actin filaments is a major determinant of vital cellular processes such as endocytosis, cytokinesis, and cell migration (1)(2)(3)(4). Specific protein assemblies, composed of various actin-binding proteins, operate in these processes to nucleate and elongate new actin filaments, arrange them into complex 3D arrays, and subsequently recycle them to replenish the G-actin pool (5).…”

mentioning

confidence: 99%

Distinct VASP tetramers synergize in the processive elongation of individual actin filaments from clustered arrays

Brühmann

Ushakov

Winterhoff

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Ena/VASP proteins act as actin polymerases that drive the processive elongation of filament barbed ends in membrane protrusions or at the surface of bacterial pathogens. Based on previous analyses of fast and slow elongating VASP proteins by in vitro total internal reflection fluorescence microscopy (TIRFM) and kinetic and thermodynamic measurements, we established a kinetic model of Ena/VASP-mediated actin filament elongation. At steady state, it entails that tetrameric VASP uses one of its arms to processively track growing filament barbed ends while three G-actin-binding sites (GABs) on other arms are available to recruit and deliver monomers to the filament tip, suggesting that VASP operates as a single tetramer in solution or when clustered on a surface, albeit processivity and resistance toward capping protein (CP) differ dramatically between both conditions. Here, we tested the model by variation of the oligomerization state and by increase of the number of GABs on individual polypeptide chains. In excellent agreement with model predictions, we show that in solution the rates of filament elongation directly correlate with the number of free GABs. Strikingly, however, irrespective of the oligomerization state or presence of additional GABs, filament elongation on a surface invariably proceeded with the same rate as with the VASP tetramer, demonstrating that adjacent VASP molecules synergize in the elongation of a single filament. Additionally, we reveal that actin ATP hydrolysis is not required for VASP-mediated filament assembly. Finally, we show evidence for the requirement of VASP to form tetramers and provide an amended model of processive VASPmediated actin assembly in clustered arrays.actin | Ena/VASP | TIRF | cluster | formin

show abstract

mentioning

confidence: 99%

Distinct VASP tetramers synergize in the processive elongation of individual actin filaments from clustered arrays

Brühmann

Ushakov

Winterhoff

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…In the past few decades, cellular biologists have directed thorough attention to directional migration 7,8 and cell adhesion 9 , in which actin-assembly plays a pivotal role, resulting in the elucidation of a number of key molecules involved in cell motility. These include actin-related protein 2 / 3 Arp 2 / 3 complex, RAS-related C3 botulinus toxin substrate RAC , suppressor of cAMP receptor / WiskottAldrich syndrome protein SCAR / WASP , Rho guanine nucleotide exchange factor GMF , and enabled / vasodilator-stimulated phosphoprotein ENA / VASP [10][11][12][13] . Morphologically, the formation of membranous protrusions lamellipodia and elongated protrusions filopodia , is essential in directional migration.…”

Section: Shinyokohama Daiichi Clinicmentioning

confidence: 99%

Ultrastructural Aspects of Rat Renal Tubular Epithelium <i>in Vitro</i>: Scanning Electron Microscopy （SEM） Analyses at Various Stages of Culture

:筆頭著者

Morita

Inui

et al. 2017

Showa Univ J Med Sci

View full text Add to dashboard Cite

: Renal tubular epithelial cells are capable of regenerating themselves after severe injury. In cellular regeneration, cell migration plays a crucial role. Previous studies have demonstrated that changes in cellular morphology, including the formation of lamellipodia, are very important in cell migration. However, the ultrastructure of a migrating cell largely remains undescribed. In the present study, we applied scanning electron microscopy techniques to cultured cells, and observed fine ultrastructural changes in cultured renal tubular epithelium during migration. We found that there were small sphere-like structures and / or microvilli on the cell surface of oating epithelia, that leaf-like structures closely resembling lamellipodia developed circumferentially in the early stages of culture, and that long and branched lopodia developed that were much larger in diameter compared to lopodia at earlier stages. To the best of our knowledge, these ndings are new, and may contribute to the development of a new therapeutic strategy for severe tubular damage of the kidney.

show abstract

“…During the next steps of cell migration, the cell body moves forward in the migration direction and releases the cell-substrate adhesion at the cell rear [4]. At the cell front, the membrane begins as a flat cellular protrusion that is powered by actin polymerization and can be visualized by phase contrast microscopy as dark waves, which are called membrane ruffles [4,5]. Lamellipodia are sheet-like projections formed at the leading edge of many migrating cells, including fibroblasts, immune cells, neural crest cells, and melanoblasts [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…At the cell front, the membrane begins as a flat cellular protrusion that is powered by actin polymerization and can be visualized by phase contrast microscopy as dark waves, which are called membrane ruffles [4,5]. Lamellipodia are sheet-like projections formed at the leading edge of many migrating cells, including fibroblasts, immune cells, neural crest cells, and melanoblasts [5,6]. This review will discuss the role of FA and its effect on lamellipodia dynamics in understanding adhesion-dependent cell migration.…”

Section: Introductionmentioning

confidence: 99%

Role of Focal Adhesions in Lamellipodia Dynamics

Yeo¹

2015

J Biotechnol Biomater

View full text Add to dashboard Cite

Focal adhesions (FAs) are multi-protein structures containing integrin that serve as a focal point for the association between the extracellular matrix (ECM) and actin cytoskeleton. After cells adhere to the ECM, the cell membrane forms filopodia and lamellipodia. Cells deficient in FA complexes show reduced lamellipodia dynamics and this deficiency influences cell migration. Lamellipodia dynamics have distinguishable stages of lamellipodia protrusion, retraction, and persistence. Particularly, cells with decreasing or absent FA formation commonly show longer persistence time as analyzed using computer-assisted stroboscopic analysis. These results indicate that after cells adhere to the substratum, the reduced lamellipodia dynamics associated with defective FA formation influences cell motility.Cell migration plays a central role in many physiological and pathological processes including embryogenesis, inflammatory response, wound healing, and metastasis. Cell migration is a distinctive, integrative, multistep process including formation of the cell adhesion, membrane protrusion at the front area, cell body contraction, and tail detachment [1]. Cell adhesion utilizes focal adhesions (FAs), fibrillary adhesions, and podosomes [2] to link the extracellular matrix (ECM) and various cytoplasmic proteins. After cells adhere to the ECM, the membrane begins filopodium formation and lamellipodium extension at the front edge of the cell. These are driven by actin polymerization and microtubule dynamics [3]. During the next steps of cell migration, the cell body moves forward in the migration direction and releases the cell-substrate adhesion at the cell rear [4]. At the cell front, the membrane begins as a flat cellular protrusion that is powered by actin polymerization and can be visualized by phase contrast microscopy as dark waves, which are called membrane ruffles [4,5]. Lamellipodia are sheet-like projections formed at the leading edge of many migrating cells, including fibroblasts, immune cells, neural crest cells, and melanoblasts [5,6]. This review will discuss the role of FA and its effect on lamellipodia dynamics in understanding adhesion-dependent cell migration. FAs are highly dynamic structures that form at sites of membrane contact with the ECM and associate with many cellular proteins known as FA complexes, including vinculin, focal adhesion kinase (FAK), Src family kinases (SFKs), paxillin, p130CAS (Crk-associate substrate), and Crk [2,7]. Deficiency of FA complexes in mouse embryo fibroblasts (MEFs) results in severe defects in cell spreading and culminates in embryonic death. For example, FAK-null MEFs show mesodermal defects in the late phase of gastrulation and have a delay in cell migration in vitro [8,9]. Deficiency of p130CAS causes severe defects in cell spreading [9,10]. In SYF cells (deficient for Src, Yes, and Fyn), MEFs show a decreased formation of FAs, which results in severe developmental defects, lethality, and delayed cell migration [11][12][13]. Additionally, Crknull mice die dur...

show abstract

Steering cell migration: lamellipodium dynamics and the regulation of directional persistence

Cited by 524 publications

References 206 publications

Distinct VASP tetramers synergize in the processive elongation of individual actin filaments from clustered arrays

Distinct VASP tetramers synergize in the processive elongation of individual actin filaments from clustered arrays

Ultrastructural Aspects of Rat Renal Tubular Epithelium <i>in Vitro</i>: Scanning Electron Microscopy （SEM） Analyses at Various Stages of Culture

Role of Focal Adhesions in Lamellipodia Dynamics

Contact Info

Product

Resources

About