Browse
Submit Data
Databases
API
Help

Dataset Information

13 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Four different mechanisms for switching cell polarity.

ABSTRACT: The mechanisms and design principles of regulatory systems establishing stable polarized protein patterns within cells are well studied. However, cells can also dynamically control their cell polarity. Here, we ask how an upstream signaling system can switch the orientation of a polarized pattern. We use a mathematical model of a core polarity system based on three proteins as the basis to study different mechanisms of signal-induced polarity switching. The analysis of this model reveals four general classes of switching mechanisms with qualitatively distinct behaviors: the transient oscillator switch, the reset switch, the prime-release switch, and the push switch. Each of these regulatory mechanisms effectively implements the function of a spatial toggle switch, however with different characteristics in their nonlinear and stochastic dynamics. We identify these characteristics and also discuss experimental signatures of each type of switching mechanism.

SUBMITTER: Tostevin F

PROVIDER: S-EPMC7861558 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Four different mechanisms for switching cell polarity.

Tostevin Filipe F Wigbers Manon M Søgaard-Andersen Lotte L Gerland Ulrich U

PLoS computational biology 20210119 1

The mechanisms and design principles of regulatory systems establishing stable polarized protein patterns within cells are well studied. However, cells can also dynamically control their cell polarity. Here, we ask how an upstream signaling system can switch the orientation of a polarized pattern. We use a mathematical model of a core polarity system based on three proteins as the basis to study different mechanisms of signal-induced polarity switching. The analysis of this model reveals four ge ...[more]

PMID: 33465073

Similar Datasets

Generation of spatial patterns through cell polarity switching.

Project description:The mechanisms that generate dynamic spatial patterns within proliferating tissues are poorly understood, largely because of difficulties in unravelling interactions between cell specification, polarity, asymmetric division, rearrangements, and growth. We address this problem for stomatal spacing in plants, which offer the simplifying advantage that cells do not rearrange. By tracking lineages and gene activities over extended periods, we show that limited stem cell behavior of stomatal precursors depends on maintenance of the SPEECHLESS (SPCH) transcription factor in single daughter cells. Modeling shows how this property can lead to observed stereotypical stomata lineages through a postmitotic polarity-switching mechanism. The model predicts the location of a polarity determinant BASL over multiple divisions, which we validate experimentally. Our results highlight the dynamic two-way interactions between stem cells and their neighborhood during developmental patterning.

| S-EPMC3383840 | biostudies-literature

Internalization of multiple cells during C. elegans gastrulation depends on common cytoskeletal mechanisms but different cell polarity and cell fate regulators.

Project description:Understanding the links between developmental patterning mechanisms and force-producing cytoskeletal mechanisms is a central goal in studies of morphogenesis. Gastrulation is the first morphogenetic event in the development of many organisms. Gastrulation involves the internalization of surface cells, often driven by the contraction of actomyosin networks that are deployed with spatial precision-both in specific cells and in a polarized manner within each cell. These cytoskeletal mechanisms rely on different cell fate and cell polarity regulators in different organisms. Caenorhabditis elegans gastrulation presents an opportunity to examine the extent to which diverse mechanisms may be used by dozens of cells that are internalized at distinct times within a single organism. We identified 66 cells that are internalized in C. elegans gastrulation, many of which were not known previously to gastrulate. To gain mechanistic insights into how these cells internalize, we genetically manipulated cell fate, cell polarity and cytoskeletal regulators and determined the effects on cell internalization. We found that cells of distinct lineages depend on common actomyosin-based mechanisms to gastrulate, but different cell fate regulators, and, surprisingly, different cell polarity regulators. We conclude that diverse cell fate and cell polarity regulators control common mechanisms of morphogenesis in C. elegans. The results highlight the variety of developmental patterning mechanisms that can be associated with common cytoskeletal mechanisms in the morphogenesis of an animal embryo.

| S-EPMC3022094 | biostudies-literature

Physical mechanisms redirecting cell polarity and cell shape in fission yeast.

Project description:The cylindrical rod shape of the fission yeast Schizosaccharomyces pombe is organized and maintained by interactions between the microtubule, cell membrane, and actin cytoskeleton [1]. Mutations affecting any components in this pathway lead to bent, branched, or round cells [2]. In this context, the cytoskeleton controls cell polarity and thus dictates cell shape. Here, we use soft-lithography techniques to construct microfluidic channels to control cell shape. We show that when wild-type rod-shaped cells are physically forced to grow in a bent fashion, they will reorganize their cytoskeleton and redirect cell polarity to make new ectopic cell tips. Moreover, when bent or round mutant cells are physically forced to conform to the wild-type rod-shape, they will reverse their mutational phenotypes by reorganizing their cytoskeleton to maintain proper wild-type-like localization of microtubules, cell-membrane proteins, and actin. Our study provides direct evidence that the cytoskeleton controls cell polarity and cell shape and demonstrates that cell shape also controls the organization of the cytoskeleton in a feedback loop. We present a model of the feedback loop to explain how fission yeast maintain a rod shape and how perturbation of specific parameters of the loop can lead to different cell shapes.

| S-EPMC2997722 | biostudies-literature

Cellular mechanisms for cargo delivery and polarity maintenance at different polar domains in plant cells.

Project description:The asymmetric localization of proteins in the plasma membrane domains of eukaryotic cells is a fundamental manifestation of cell polarity that is central to multicellular organization and developmental patterning. In plants, the mechanisms underlying the polar localization of cargo proteins are still largely unknown and appear to be fundamentally distinct from those operating in mammals. Here, we present a systematic, quantitative comparative analysis of the polar delivery and subcellular localization of proteins that characterize distinct polar plasma membrane domains in plant cells. The combination of microscopic analyses and computational modeling revealed a mechanistic framework common to diverse polar cargos and underlying the establishment and maintenance of apical, basal, and lateral polar domains in plant cells. This mechanism depends on the polar secretion, constitutive endocytic recycling, and restricted lateral diffusion of cargos within the plasma membrane. Moreover, our observations suggest that polar cargo distribution involves the individual protein potential to form clusters within the plasma membrane and interact with the extracellular matrix. Our observations provide insights into the shared cellular mechanisms of polar cargo delivery and polarity maintenance in plant cells.

| S-EPMC4950145 | biostudies-literature

Antioxidant mechanisms and products of four 4',5,7-trihydroxyflavonoids with different structural types.

Project description:4',5,7-OHs are common substituents of natural flavonoids, a type of effective phenolic antioxidant. However, the antioxidant processes between 4',5,7-trihydroxyflavonoids with different structural types have not been compared systematically, and the antioxidant products are challenging to determine. This study compared four 4',5,7-trihydroxyflavonoids, including apigenin, genistein, kaempferol, and naringenin. In quantum chemical analyses, the four 4',5,7-trihydroxyflavonoids showed different thermodynamic properties, and the C4'-OH (or C3-OH of kaempferol) possessed the strongest activity. Moreover, the reaction rate constants were larger when a hydrogen atom was transferred from C4'-OH (or C3-OH of kaempferol) than from C5-OH. When different atoms were linked to 2,2-diphenyl-1-picrylhydrazyl radical (DPPH˙), the C3'-DPPH adducts showed the smallest energy. In experimental assays, the scavenging ability for neutral free radicals, radical cations, and radical anions was negatively correlated with the corresponding theoretical parameters. Finally, mass spectroscopy detected the apigenin-DPPH˙, genistein-DPPH˙, and naringenin-DPPH˙ adduct peaks. In conclusion, the structural type of 4',5,7-trihydroxyflavonoids can affect the antioxidant ability, site, and speed, but not the mechanism. After hydrogen abstraction at C4'-OH, 4',5,7-trihydroxyflavones, 4',5,7-trihydroxyisoflavones, and 4',5,7-trihydroxyflavanones will produce antioxidant products via C3'-radical linking.

| S-EPMC9890593 | biostudies-literature

Effects of Four Different Regulatory Mechanisms on the Dynamics of Gene Regulatory Cascades.

Project description:Gene regulatory cascades (GRCs) are common motifs in cellular molecular networks. A given logical function in these cascades, such as the repression of the activity of a transcription factor, can be implemented by a number of different regulatory mechanisms. The potential consequences for the dynamic performance of the GRC of choosing one mechanism over another have not been analysed systematically. Here, we report the construction of a synthetic GRC in Escherichia coli, which allows us for the first time to directly compare and contrast the dynamics of four different regulatory mechanisms, affecting the transcription, translation, stability, or activity of a transcriptional repressor. We developed a biologically motivated mathematical model which is sufficient to reproduce the response dynamics determined by experimental measurements. Using the model, we explored the potential response dynamics that the constructed GRC can perform. We conclude that dynamic differences between regulatory mechanisms at an individual step in a GRC are often concealed in the overall performance of the GRC, and suggest that the presence of a given regulatory mechanism in a certain network environment does not necessarily mean that it represents a single optimal evolutionary solution.

| S-EPMC4505322 | biostudies-literature

A qrr noncoding RNA deploys four different regulatory mechanisms to optimize quorum-sensing dynamics.

Project description:Quorum sensing is a cell-cell communication process that bacteria use to transition between individual and social lifestyles. In vibrios, homologous small RNAs called the Qrr sRNAs function at the center of quorum-sensing pathways. The Qrr sRNAs regulate multiple mRNA targets including those encoding the quorum-sensing regulatory components luxR, luxO, luxM, and aphA. We show that a representative Qrr, Qrr3, uses four distinct mechanisms to control its particular targets: the Qrr3 sRNA represses luxR through catalytic degradation, represses luxM through coupled degradation, represses luxO through sequestration, and activates aphA by revealing the ribosome binding site while the sRNA itself is degraded. Qrr3 forms different base-pairing interactions with each mRNA target, and the particular pairing strategy determines which regulatory mechanism occurs. Combined mathematical modeling and experiments show that the specific Qrr regulatory mechanism employed governs the potency, dynamics, and competition of target mRNA regulation, which in turn, defines the overall quorum-sensing response.

| S-EPMC4313533 | biostudies-other

Structural comparison of four different antibodies interacting with human papillomavirus 16 and mechanisms of neutralization.

Project description:Cryo-electron microscopy (cryo-EM) was used to solve the structures of human papillomavirus type 16 (HPV16) complexed with fragments of antibody (Fab) from three different neutralizing monoclonals (mAbs): H16.1A, H16.14J, and H263.A2. The structure-function analysis revealed predominantly monovalent binding of each Fab with capsid interactions that involved multiple loops from symmetry related copies of the major capsid protein. The residues identified in each Fab-virus interface map to a conformational groove on the surface of the capsomer. In addition to the known involvement of the FG and HI loops, the DE loop was also found to constitute the core of each epitope. Surprisingly, the epitope mapping also identified minor contributions by EF and BC loops. Complementary immunological assays included mAb and Fab neutralization. The specific binding characteristics of mAbs correlated with different neutralizing behaviors in pre- and post-attachment neutralization assays.

| S-EPMC4516578 | biostudies-literature

The Drosophila Cadherin Fat regulates tissue size and planar cell polarity through different domains.

Project description:The Drosophila Cadherin Fat (Ft) has been identified as a crucial regulator of tissue size and Planar Cell Polarity (PCP). However, the precise mechanism by which Ft regulates these processes remains unclear. In order to advance our understanding of the action of Ft, we have sought to identify the crucial Ft effector domains. Here we report that a small region of the Ft cytoplasmic domain (H2 region) is both necessary and sufficient, when membrane localized, to support viability and prevent tissue overgrowth. Interestingly, the H2 region is dispensable for regulating PCP signaling, whereas the mutant Ft lacking the H2 region is fully capable of directing PCP. This result suggests that Ft's roles in PCP signaling and tissue size control are separable, and each can be carried out independently. Surprisingly, the crucial regions of Ft identified in our structure-function study do not overlap with the previously reported interaction regions with Atrophin, Dco, or Lowfat.

| S-EPMC3647076 | biostudies-literature

Asymmetric localization of Vangl2 and Fz3 indicate novel mechanisms for planar cell polarity in mammals.

Project description:Planar cell polarity (PCP) is a process in which cells develop with uniform orientation within the plane of an epithelium. To begin to elucidate the mechanisms of PCP in vertebrates, the localization of the protein Vangl2 (Van Gogh-like) was determined during the development of the mammalian cochlea. Results indicate that Vangl2 becomes asymmetrically localized to specific cell-cell boundaries along the axis of polarization and that this asymmetry is lost in PCP mutants. In addition, PDZ2 (postsynaptic density/Discs large/zona occludens 1), PDZ3, and PDZ4 of the PCP protein Scrb1 (Scribble) are shown to bind to the C-terminal PDZ binding domain of Vangl2, suggesting that Scrb1 plays a direct role in asymmetric targeting of Vangl2. Finally, Fz3 (Frizzled), a newly demonstrated mediator of PCP, is also asymmetrically localized in a pattern that matches that of Vangl2. The presence and asymmetry of Fz3 at the membrane is shown to be dependent on Vangl2. This result suggests a role for Vangl2 in the targeting or anchoring of Fz3, a hypothesis strengthened by the existence of a physical interaction between the two proteins. Together, our data support the idea that protein asymmetry plays an important role in the development of PCP, but the colocalization and interaction of Fz3 and Vangl2 suggests that novel PCP mechanisms exist in vertebrates.

| S-EPMC6674235 | 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