Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A plasma membrane template for macropinocytic cups.

ABSTRACT: Macropinocytosis is a fundamental mechanism that allows cells to take up extracellular liquid into large vesicles. It critically depends on the formation of a ring of protrusive actin beneath the plasma membrane, which develops into the macropinocytic cup. We show that macropinocytic cups in Dictyostelium are organised around coincident intense patches of PIP₃, active Ras and active Rac. These signalling patches are invariably associated with a ring of active SCAR/WAVE at their periphery, as are all examined structures based on PIP₃ patches, including phagocytic cups and basal waves. Patch formation does not depend on the enclosing F-actin ring, and patches become enlarged when the RasGAP NF1 is mutated, showing that Ras plays an instructive role. New macropinocytic cups predominantly form by splitting from existing ones. We propose that cup-shaped plasma membrane structures form from self-organizing patches of active Ras/PIP₃, which recruit a ring of actin nucleators to their periphery.

SUBMITTER: Veltman DM

PROVIDER: S-EPMC5154761 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

A plasma membrane template for macropinocytic cups.

Veltman Douwe M DM Williams Thomas D TD Bloomfield Gareth G Chen Bi-Chang BC Betzig Eric E Insall Robert H RH Kay Robert R RR

eLife 20161213

Macropinocytosis is a fundamental mechanism that allows cells to take up extracellular liquid into large vesicles. It critically depends on the formation of a ring of protrusive actin beneath the plasma membrane, which develops into the macropinocytic cup. We show that macropinocytic cups in <i>Dictyostelium</i> are organised around coincident intense patches of PIP<sub>3</sub>, active Ras and active Rac. These signalling patches are invariably associated with a ring of active SCAR/WAVE at their ...[more]

PMID: 27960076

Similar Datasets

Three-dimensional morphodynamic simulations of macropinocytic cups.

Project description:Macropinocytosis refers to the non-specific uptake of extracellular fluid, which plays ubiquitous roles in cell growth, immune surveillance, and virus entry. Despite its widespread occurrence, it remains unclear how its initial cup-shaped plasma membrane extensions form without any external solid support, as opposed to the process of particle uptake during phagocytosis. Here, by developing a computational framework that describes the coupling between the bistable reaction-diffusion processes of active signaling patches and membrane deformation, we demonstrated that the protrusive force localized to the edge of the patches can give rise to a self-enclosing cup structure, without further assumptions of local bending or contraction. Efficient uptake requires a balance among the patch size, magnitude of protrusive force, and cortical tension. Furthermore, our model exhibits cyclic cup formation, coexistence of multiple cups, and cup-splitting, indicating that these complex morphologies self-organize via a common mutually-dependent process of reaction-diffusion and membrane deformation.

| S-EPMC8560551 | biostudies-literature

Coordinated Ras and Rac Activity Shapes Macropinocytic Cups and Enables Phagocytosis of Geometrically Diverse Bacteria.

Project description:Engulfment of extracellular material by phagocytosis or macropinocytosis depends on the ability of cells to generate specialized cup-shaped protrusions. To effectively capture and internalize their targets, these cups are organized into a ring or ruffle of actin-driven protrusion encircling a non-protrusive interior domain. These functional domains depend on the combined activities of multiple Ras and Rho family small GTPases, but how their activities are integrated and differentially regulated over space and time is unknown. Here, we show that the amoeba Dictyostelium discoideum coordinates Ras and Rac activity using the multidomain protein RGBARG (RCC1, RhoGEF, BAR, and RasGAP-containing protein). We find RGBARG uses a tripartite mechanism of Ras, Rac, and phospholipid interactions to localize at the protruding edge and interface with the interior of both macropinocytic and phagocytic cups. There, we propose RGBARG shapes the protrusion by expanding Rac activation at the rim while suppressing expansion of the active Ras interior domain. Consequently, cells lacking RGBARG form enlarged, flat interior domains unable to generate large macropinosomes. During phagocytosis, we find that disruption of RGBARG causes a geometry-specific defect in engulfing rod-shaped bacteria and ellipsoidal beads. This demonstrates the importance of coordinating small GTPase activities during engulfment of more complex shapes and thus the full physiological range of microbes, and how this is achieved in a model professional phagocyte.

| S-EPMC7416115 | biostudies-literature

Plasma Membrane Integrity Signaling

Project description:To understand the transcriptional response of mammalian cells to plasma membrane stress we induced partial loss of plasmid membrane integrity by chemogenetic induction of pore forming proteins (Gasderimin and MLKL) or treatment with the detergent digitonin. We monitored transcription with mRNAseq in the immediate hours after plasma membrane damage and identified conserved transcriptional programs.

2021-10-04 | GSE166538 | GEO

Local Membrane Curvature Pins and Guides Excitable Membrane Waves in Chemotactic and Macropinocytic Cells - Biomedical Insights From an Innovative Simple Model.

Project description:PIP3 dynamics observed in membranes are responsible for the protruding edge formation in cancer and amoeboid cells. The mechanisms that maintain those PIP3 domains in three-dimensional space remain elusive, due to limitations in observation and analysis techniques. Recently, a strong relation between the cell geometry, the spatial confinement of the membrane, and the excitable signal transduction system has been revealed by Hörning and Shibata (2019) using a novel 3D spatiotemporal analysis methodology that enables the study of membrane signaling on the entire membrane (Hörning and Shibata, 2019). Here, using 3D spatial fluctuation and phase map analysis on actin polymerization inhibited Dictyostelium cells, we reveal a spatial asymmetry of PIP3 signaling on the membrane that is mediated by the contact perimeter of the plasma membrane - the spatial boundary around the cell-substrate adhered area on the plasma membrane. We show that the contact perimeter guides PIP3 waves and acts as a pinning site of PIP3 phase singularities, that is, the center point of spiral waves. The contact perimeter serves as a diffusion influencing boundary that is regulated by a cell size- and shape-dependent curvature. Our findings suggest an underlying mechanism that explains how local curvature can favor actin polymerization when PIP3 domains get pinned at the curved protrusive membrane edges in amoeboid cells.

| S-EPMC8479871 | biostudies-literature

Plasma Membrane Integrity Signaling

Project description:Plasma Membrane Integrity Signaling

| PRJNA701242 | ENA

Microtopographical guidance of macropinocytic signaling patches.

Project description:In fast-moving cells such as amoeba and immune cells, dendritic actin filaments are spatiotemporally regulated to shape large-scale plasma membrane protrusions. Despite their importance in migration, as well as in particle and liquid ingestion, how their dynamics are affected by micrometer-scale features of the contact surface is still poorly understood. Here, through quantitative image analysis of Dictyostelium on microfabricated surfaces, we show that there is a distinct mode of topographical guidance directed by the macropinocytic membrane cup. Unlike other topographical guidance known to date that depends on nanometer-scale curvature sensing protein or stress fibers, the macropinocytic membrane cup is driven by the Ras/PI3K/F-actin signaling patch and its dependency on the micrometer-scale topographical features, namely PI3K/F-actin-independent accumulation of Ras-GTP at the convex curved surface, PI3K-dependent patch propagation along the convex edge, and its actomyosin-dependent constriction at the concave edge. Mathematical model simulations demonstrate that the topographically dependent initiation, in combination with the mutually defining patch patterning and the membrane deformation, gives rise to the topographical guidance. Our results suggest that the macropinocytic cup is a self-enclosing structure that can support liquid ingestion by default; however, in the presence of structured surfaces, it is directed to faithfully trace bent and bifurcating ridges for particle ingestion and cell guidance.

| S-EPMC8685668 | biostudies-literature

No superior performance of hydroxyapatite-coated acetabular cups over porous-coated cups.

Project description:Background and purposeHydroxyapatite (HA) coating is believed to improve bone-implant ingrowth and long-term survival of prostheses. Recent studies, however, have challenged this view. Furthermore, HA particles may produce third-body wear and initiate aseptic loosening of implants. We report the performance of HA- and porous-coated acetabular cups in a prospective randomized trial.MethodsThis was an 8-year follow-up study of our previously published prospective randomized study to compare clinical outcomes, survival, periprosthetic bone mineral density, migration, and wear rates of HA- and porous-coated acetabular cups. Dual X-ray absorptiometry (DXA) and Ein Bild Roentgen Analyse (EBRA) measurements were used. 100 patients who underwent unilateral cementless total hip arthroplasty were randomized to either porous-coated cups or HA-coated cups. Patients were examined preoperatively and at 3, 6, and 9 months, and also 1, 3, and 8 years after surgery. 81 patients were available for 8-year follow-up, 40 with porous-coated cups and 41 with HA-coated cups.ResultsAge, sex, bone mineral density, and clinical results (Harris hip score) were similar in the 2 groups. The survival, wear, and migration patterns of the cups were also similar in both groups. The results of periprosthetic bone mineral density scans in region of interest 2 was in favor of the porous-coated cups, but there were no differences between the 2 groups in all the remaining regions of interest.InterpretationHA coating had no statistically significant effect on clinical results, survival, wear, or migration at the 8-year follow-up.

| S-EPMC3851667 | biostudies-literature

Bullous pemphigoid IgG induces BP180 internalization via a macropinocytic pathway.

Project description:Bullous pemphigoid (BP) is an autoimmune blistering skin disease induced by pathogenic autoantibodies against a type II transmembrane protein (BP180, collagen type XVII, or BPAG2). In animal models, BP180 autoantibody-antigen interaction appears insufficient to develop blisters, but involvement of complement and neutrophils is required. However, cultured keratinocytes treated with BP-IgG exhibit a reduction in the adhesive strength and a loss of expression of BP180, suggesting that the autoantibodies directly affect epidermal cell-extracellular matrix integrity. In this study, we explored the consequences of two distinct epithelial cells treated with BP-IgG, particularly the fate of BP180. First, we followed the distribution of green fluorescent protein-tagged BP180 in an epithelial cell line, 804G, and normal human epidermal keratinocytes after autoantibody clustering. After BP-IgG treatment, the adhesive strength of the cells to their substrate was decreased, and BP180 was internalized in both cell types, together with the early endosomal antigen-1. By using various endocytosis inhibitors and a fluid-uptake assay, we demonstrated that BP-IgG-induced BP180 internalization is mediated via a macropinocytic pathway. Moreover, a macropinocytosis inhibitor rescued a BP-IgG-induced reduction in the adhesive strength of the cells from their substrate. The results of this study suggest that BP180 internalization induced by BP-IgG plays an important role in the initiation of disease pathogenesis.

| S-EPMC3590760 | biostudies-literature

Transcript profiling of Arabidopsis plasma membrane proton pump mutants

Project description:Plasma membrane proton pump maintains proton electrochemical gradient and provides energy to secondary transporters. Arabidopsis mutant plants with reduced proton pump activity grow normal under ideal growth conditions; however their growth are reduced compared with wildtype plants when placed under the conditions that stress on protonmotive force (high external pH or high external potassium). Seedlings of wildtype, aha1, and aha2 mutant plants were grown under ideal growth condition. Total RNA from those seedlings were subjected to transcriptome analyses using Affymetrix Gene Chip.

2015-04-01 | E-GEOD-34202 | biostudies-arrayexpress

Shaping cups into phagosomes and macropinosomes.

Project description:The ingestion of particles or cells by phagocytosis and of fluids by macropinocytosis requires the formation of large endocytic vacuolar compartments inside cells by the organized movements of membranes and the actin cytoskeleton. Fc-receptor-mediated phagocytosis is guided by the zipper-like progression of local, receptor-initiated responses that conform to particle geometry. By contrast, macropinosomes and some phagosomes form with little or no guidance from receptors. The common organizing structure is a cup-shaped invagination of the plasma membrane that becomes the phagosome or macropinosome. Recent studies, focusing on the physical properties of forming cups, indicate that a feedback mechanism regulates the signal transduction of phagocytosis and macropinocytosis.

| S-EPMC2851551 | 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