Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Spatial regulation of RhoC activity defines protrusion formation in migrating cells.

ABSTRACT: Protrusion formation is the first step that precedes cell movement of motile cells. Spatial control of actin polymerization is necessary to achieve directional protrusion during cell migration. Here we show that the spatial coordinators p190RhoGEF and p190RhoGAP regulate actin polymerization during leading edge protrusions by regulating the actin barbed end distribution and amplitude. The distribution of RhoC activity and proper balance of cofilin activation achieved by p190RhoGEF and p190RhoGAP determines the direction of final protrusive activity. These findings provide a new insight into the dynamic plasticity in the amplitude and distribution of barbed ends, which can be modulated by fine-tuning RhoC activity by upstream GEFs and GAPs for directed cell motility.

SUBMITTER: Bravo-Cordero JJ

PROVIDER: S-EPMC3730245 | biostudies-other | 2013 Aug

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

Spatial regulation of RhoC activity defines protrusion formation in migrating cells.

Bravo-Cordero Jose Javier JJ Sharma Ved P VP Roh-Johnson Minna M Chen Xiaoming X Eddy Robert R Condeelis John J Hodgson Louis L

Journal of cell science 20130523 Pt 15

Protrusion formation is the first step that precedes cell movement of motile cells. Spatial control of actin polymerization is necessary to achieve directional protrusion during cell migration. Here we show that the spatial coordinators p190RhoGEF and p190RhoGAP regulate actin polymerization during leading edge protrusions by regulating the actin barbed end distribution and amplitude. The distribution of RhoC activity and proper balance of cofilin activation achieved by p190RhoGEF and p190RhoGAP ...[more]

PMID: 23704350

Similar Datasets

E-cadherin focuses protrusion formation at the front of migrating cells by impeding actin flow.

Project description:The migration of many cell types relies on the formation of actomyosin-dependent protrusions called blebs, but the mechanisms responsible for focusing this kind of protrusive activity to the cell front are largely unknown. Here, we employ zebrafish primordial germ cells (PGCs) as a model to study the role of cell-cell adhesion in bleb-driven single-cell migration in vivo. Utilizing a range of genetic, reverse genetic and mathematical tools, we define a previously unknown role for E-cadherin in confining bleb-type protrusions to the leading edge of the cell. We show that E-cadherin-mediated frictional forces impede the backwards flow of actomyosin-rich structures that define the domain where protrusions are preferentially generated. In this way, E-cadherin confines the bleb-forming region to a restricted area at the cell front and reinforces the front-rear axis of migrating cells. Accordingly, when E-cadherin activity is reduced, the bleb-forming area expands, thus compromising the directional persistence of the cells.

| S-EPMC7588466 | biostudies-literature

Regulation of protrusion, adhesion dynamics, and polarity by myosins IIA and IIB in migrating cells.

Project description:We have used isoform-specific RNA interference knockdowns to investigate the roles of myosin IIA (MIIA) and MIIB in the component processes that drive cell migration. Both isoforms reside outside of protrusions and act at a distance to regulate cell protrusion, signaling, and maturation of nascent adhesions. MIIA also controls the dynamics and size of adhesions in central regions of the cell and contributes to retraction and adhesion disassembly at the rear. In contrast, MIIB establishes front-back polarity and centrosome, Golgi, and nuclear orientation. Using ATPase- and contraction-deficient mutants of both MIIA and MIIB, we show a role for MIIB-dependent actin cross-linking in establishing front-back polarity. From these studies, MII emerges as a master regulator and integrator of cell migration. It mediates each of the major component processes that drive migration, e.g., polarization, protrusion, adhesion assembly and turnover, polarity, signaling, and tail retraction, and it integrates spatially separated processes.

| S-EPMC2064016 | biostudies-literature

Novel protein Callipygian defines the back of migrating cells.

Project description:Asymmetric protein localization is essential for cell polarity and migration. We report a novel protein, Callipygian (CynA), which localizes to the lagging edge before other proteins and becomes more tightly restricted as cells polarize; additionally, it accumulates in the cleavage furrow during cytokinesis. CynA protein that is tightly localized, or "clustered," to the cell rear is immobile, but when polarity is disrupted, it disperses throughout the membrane and responds to uniform chemoattractant stimulation by transiently localizing to the cytosol. These behaviors require a pleckstrin homology-domain membrane tether and a WD40 clustering domain, which can also direct other membrane proteins to the back. Fragments of CynA lacking the pleckstrin homology domain, which are normally found in the cytosol, localize to the lagging edge membrane when coexpressed with full-length protein, showing that CynA clustering is mediated by oligomerization. Cells lacking CynA have aberrant lateral protrusions, altered leading-edge morphology, and decreased directional persistence, whereas those overexpressing the protein display exaggerated features of polarity. Consistently, actin polymerization is inhibited at sites of CynA accumulation, thereby restricting protrusions to the opposite edge. We suggest that the mutual antagonism between CynA and regions of responsiveness creates a positive feedback loop that restricts CynA to the rear and contributes to the establishment of the cell axis.

| S-EPMC4517219 | biostudies-literature

Protein kinase A governs a RhoA-RhoGDI protrusion-retraction pacemaker in migrating cells.

Project description:The cyclical protrusion and retraction of the leading edge is a hallmark of many migrating cells involved in processes such as development, inflammation and tumorigenesis. The molecular identity of the signalling mechanisms that control these cycles has remained unknown. Here, we used live-cell imaging of biosensors to monitor spontaneous morphodynamic and signalling activities, and employed correlative image analysis to examine the role of cyclic-AMP-activated protein kinase A (PKA) in protrusion regulation. PKA activity at the leading edge is closely synchronized with rapid protrusion and with the activity of RhoA. Ensuing PKA phosphorylation of RhoA and the resulting increased interaction between RhoA and RhoGDI (Rho GDP-dissociation inhibitor) establish a negative feedback mechanism that controls the cycling of RhoA activity at the leading edge. Thus, cooperation between PKA, RhoA and RhoGDI forms a pacemaker that governs the morphodynamic behaviour of migrating cells.

| S-EPMC3746034 | biostudies-literature

PAR-1 kinase regulates epithelial detachment and directional protrusion of migrating border cells.

Project description:BackgroundMany cells that migrate during normal embryonic development or in metastatic cancer first detach from an epithelium. However, this step is often difficult to observe directly in vivo, and the mechanisms controlling the ability of cells to leave the epithelium are poorly understood. In addition, once cells detach, they must assume a migratory phenotype, involving changes in cytoskeletal and signaling dynamics. Drosophila border cells provide a model system in which a combination of forward genetics and live-cell imaging can allow researchers to investigate the cellular and molecular mechanisms of epithelial cell detachment and migration in vivo.ResultsWe identified the Drosophila homolog of the serine/threonine kinase PAR-1 (MARK/Kin1) in a screen for mutations that disrupt border cell migration. Previous studies identified two proteins, Apontic and Notch, that indirectly affect border cell detachment by regulating transcription of downstream targets. In contrast, PAR-1 directly modulates apical-basal polarity between border cells and epithelial cells to promote detachment. Furthermore, PAR-1, but not the apical polarity complex protein PAR-3, promotes the directionality of transient cell protrusions, which border cells require for sensing the chemoattractant gradient.ConclusionsWe conclude that PAR-1-dependent apical-basal polarity is required for proper detachment of migratory border cells from neighboring epithelial cells. Moreover, polarity controlled by PAR-1 influences the ability of migratory cells to sense direction, a critical feature of migration. Thus, this work reveals new insights into two distinct, but essential, steps of epithelial cell migration.

| S-EPMC2593744 | biostudies-literature

Coordination of protrusion dynamics within and between collectively migrating border cells by myosin II.

Project description:Collective cell migration is emerging as a major driver of embryonic development, organogenesis, tissue homeostasis, and tumor dissemination. In contrast to individually migrating cells, collectively migrating cells maintain cell-cell adhesions and coordinate direction-sensing as they move. While nonmuscle myosin II has been studied extensively in the context of cells migrating individually in vitro, its roles in cells migrating collectively in three-dimensional, native environments are not fully understood. Here we use genetics, Airyscan microscopy, live imaging, optogenetics, and Förster resonance energy transfer to probe the localization, dynamics, and functions of myosin II in migrating border cells of the Drosophila ovary. We find that myosin accumulates transiently at the base of protrusions, where it functions to retract them. E-cadherin and myosin colocalize at border cell-border cell contacts and cooperate to transmit directional information. A phosphomimetic form of myosin is sufficient to convert border cells to a round morphology and blebbing migration mode. Together these studies demonstrate that distinct and dynamic pools of myosin II regulate protrusion dynamics within and between collectively migrating cells and suggest a new model for the role of protrusions in collective direction sensing in vivo.

| S-EPMC6743363 | biostudies-literature

Stochastic Dynamics of Membrane Protrusion Mediated by the DOCK180/Rac Pathway in Migrating Cells.

Project description:Cell migration is regulated by processes that control adhesion to extracellular matrix (ECM) and force generation. While our fundamental understanding of how these control mechanisms are actuated at the molecular level (signal transduction) has been refined over many years, appreciation of their dynamics has grown more recently. Here, we formulate and analyze by stochastic simulation a quantitative model of signaling mediated by the integrin family of adhesion receptors. Nascent adhesions foster the activation of the small GTPase Rac by at least two distinct signaling pathways, one of which involves tyrosine phosphorylation of the scaffold protein paxillin and formation of multiprotein complexes containing the guanine nucleotide exchange factor DOCK180. Active Rac promotes protrusion of the cell's leading edge, which in turn enhances the rate of nascent adhesion nucleation; we call this feedback mechanism the core protrusion cycle. Protrusion is antagonized by stable adhesions, which form by myosin-dependent maturation of nascent adhesions, and we propose here a feedforward mechanism mediated by the tyrosine kinase c-Src by which this antagonism is regulated so as to allow transient protrusion at higher densities of ECM. We show that this "buffering of inhibition" mechanism, coupled with the core protrusion cycle, is capable of tuning the frequencies of protrusion and adhesion maturation events.

| S-EPMC2869102 | biostudies-literature

Spatial regulation of CLASP affinity for microtubules by Rac1 and GSK3beta in migrating epithelial cells.

Project description:Proteins that in cells specifically bind to growing microtubule plus ends (+TIPs) are thought to play important roles in polarization of the cytoskeleton. However, most +TIPs do not show a bias of their microtubule-binding behavior toward different subcellular regions. Here, we examine the dynamics of the +TIP CLASP in migrating PtK1 epithelial cells. We find that, although CLASPs track microtubule plus ends in the cell body, they dynamically decorate the entire microtubule lattice in the leading edge lamella and lamellipodium. Microtubule lattice binding is mediated by the COOH-terminal region of the CLASP microtubule-binding domain and is regulated downstream of Rac1. Phosphorylation of sites in the NH2-terminal part of the microtubule-binding domain by glycogen synthase kinase 3beta likely regulates the affinity of CLASPs for microtubule lattices. These results demonstrate the striking difference of the microtubule cytoskeleton in the lamella as compared with the cell body and provide the first direct observation of subcellular regulation of a microtubule-associated protein in migrating cells.

| S-EPMC2171640 | biostudies-other

A new mechanism for spatial pattern formation via lateral and protrusion-mediated lateral signalling.

Project description:Tissue organization and patterning are critical during development when genetically identical cells take on different fates. Lateral signalling plays an important role in this process by helping to generate self-organized spatial patterns in an otherwise uniform collection of cells. Recent data suggest that lateral signalling can be mediated both by junctional contacts between neighbouring cells and via cellular protrusions that allow non-neighbouring cells to interact with one another at a distance. However, it remains unclear precisely how signalling mediated by these distinct types of cell-cell contact can physically contribute to the generation of complex patterns without the assistance of diffusible morphogens or pre-patterns. To explore this question, in this work we develop a model of lateral signalling based on a single receptor/ligand pair as exemplified by Notch and Delta. We show that allowing the signalling kinetics to differ at junctional versus protrusion-mediated contacts, an assumption inspired by recent data which show that the cleavage of Notch in several systems requires both Delta binding and the application of mechanical force, permits individual cells to act to promote both lateral activation and lateral inhibition. Strikingly, under this model, in which Delta can sequester Notch, a variety of patterns resembling those typical of reaction-diffusion systems is observed, together with more unusual patterns that arise when we consider changes in signalling kinetics, and in the length and distribution of protrusions. Importantly, these patterns are self-organizing-so that local interactions drive tissue-scale patterning. Together, these data show that protrusions can, in principle, generate different types of patterns in addition to contributing to long-range signalling and to pattern refinement.

| S-EPMC5134009 | biostudies-literature

Cytokinesis defines a spatial landmark for hepatocyte polarization and apical lumen formation.

Project description:By definition, all epithelial cells have apical-basal polarity, but it is unclear how epithelial polarity is acquired and how polarized cells engage in tube formation. Here, we show that hepatocyte polarization is linked to cytokinesis using the rat hepatocyte cell line Can 10. Before abscission, polarity markers are delivered to the site of cell division in a strict spatiotemporal order. Immediately after abscission, daughter cells remain attached through a unique disc-shaped structure, which becomes the site for targeted exocytosis, resulting in the formation of a primitive bile canaliculus. Subsequently, oriented cell division and asymmetric cytokinesis occur at the bile canaliculus midpoint, resulting in its equal partitioning into daughter cells. Finally, successive cycles of oriented cell division and asymmetric cytokinesis lead to the formation of a tubular bile canaliculus, which is shared by two rows of hepatocytes. These findings define a novel mechanism for cytokinesis-linked polarization and tube formation, which appears to be broadly conserved in diverse cell types.

| S-EPMC4038943 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data