Browse
Submit Data
Databases
API
Help

Dataset Information

4 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A G alpha-dependent pathway that antagonizes multiple chemoattractant responses that regulate directional cell movement.

ABSTRACT: Chemotactic cells, including neutrophils and Dictyostelium discoideum, orient and move directionally in very shallow chemical gradients. As cells polarize, distinct structural and signaling components become spatially constrained to the leading edge or rear of the cell. It has been suggested that complex feedback loops that function downstream of receptor signaling integrate activating and inhibiting pathways to establish cell polarity within such gradients. Much effort has focused on defining activating pathways, whereas inhibitory networks have remained largely unexplored. We have identified a novel signaling function in Dictyostelium involving a Galpha subunit (Galpha9) that antagonizes broad chemotactic response. Mechanistically, Galpha9 functions rapidly following receptor stimulation to negatively regulate PI3K/PTEN, adenylyl cyclase, and guanylyl cyclase pathways. The coordinated activation of these pathways is required to establish the asymmetric mobilization of actin and myosin that typifies polarity and ultimately directs chemotaxis. Most dramatically, cells lacking Galpha9 have extended PI(3,4,5)P(3), cAMP, and cGMP responses and are hyperpolarized. In contrast, cells expressing constitutively activated Galpha9 exhibit a reciprocal phenotype. Their second message pathways are attenuated, and they have lost the ability to suppress lateral pseudopod formation. Potentially, functionally similar Galpha-mediated inhibitory signaling may exist in other eukaryotic cells to regulate chemoattractant response.

SUBMITTER: Brzostowski JA

PROVIDER: S-EPMC387420 | biostudies-other | 2004 Apr

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Wnt5b-Ryk pathway provides directional signals to regulate gastrulation movement.

Project description:Noncanonical Wnts are largely believed to act as permissive cues for vertebrate cell movement via Frizzled (Fz). In addition to Fz, Wnt ligands are known to regulate neurite outgrowth through an alternative receptor related to tyrosine kinase (Ryk). However, Wnt-Ryk signaling during embryogenesis is less well characterized. In this study, we report a role for Wnt5b as an instructive cue to regulate gastrulation movements through Ryk. In zebrafish, Ryk deficiency impairs Wnt5b-induced Ca(2+) activity and directional cell movement. Wnt5b-Ryk signaling promotes polarized cell protrusions. Upon Wnt5b stimulation, Fz2 but not Ryk recruits Dishevelled to the cell membrane, suggesting that Fz2 and Ryk mediate separate pathways. Using co-culture assays to generate directional Wnt5b cues, we demonstrate that Ryk-expressing cells migrate away from the Wnt5b source. We conclude that full-length Ryk conveys Wnt5b signals in a directional manner during gastrulation.

| S-EPMC2930277 | biostudies-literature

Actin-dependent plastid movement is required for motive force generation in directional nuclear movement in plants.

Project description:Nuclear movement and positioning are indispensable for most cellular functions. In plants, strong light-induced chloroplast movement to the side walls of the cell is essential for minimizing damage from strong visible light. Strong light-induced nuclear movement to the side walls also has been suggested to play an important role in minimizing damage from strong UV light. Although both movements are regulated by the same photoreceptor, phototropin, the precise cytoskeleton-based force generation mechanism for nuclear movement is unknown, in contrast to the short actin-based mechanism of chloroplast movement. Here we show that actin-dependent movement of plastids attached to the nucleus is essential for light-induced nuclear movement in the Arabidopsis leaf epidermal cell. We found that nuclei are always associated with some plastids, and that light-induced nuclear movement is correlated with the dynamics of short actin filaments associated with plastids. Indeed, nuclei without plastid attachments do not exhibit blue light-induced directional movement. Our results demonstrate that nuclei are incapable of autonomously moving in response to light, whereas attached plastids carry nuclei via the short actin filament-based movement. Thus, the close association between nuclei and plastids is essential for their cooperative movements and functions.

| S-EPMC3964046 | biostudies-literature

Growth, lifetime, directional movement and myosin-dependent motility of mutant keratin granules in cultured cells.

Project description:Intermediate filament polypeptides (IFPs) are prominent components of cytoplasmic aggregates, which are pathognomonic for multiple diseases. Recent observations in cultured cells suggest that they are dynamic and subject to regulated turnover. The emerging concept is that multiple factors contribute to motility and turnover of IFP-containing aggregates. To understand their relative contribution, quantitative tools are needed. The current study addresses this need using epithelial cells producing mutant keratin IFPs that have been identified as the cause of the hereditary blister-forming skin disease epidermolysis bullosa simplex. Digital image analysis of individual granules allowed mapping of their complete life cycle, with information on multiple characteristics at any given time-point. The deduced signet features revealed rapid granule fusion and directed transport from the periphery towards the cell centre, and a limited, ~?30 min lifetime with a slow, continuous growth phase followed by fast disassembly. As paradigmatic proof-of-principle, we demonstrate that inhibition of myosin II selectively reduces granule movement, linking keratin granule motility to retrograde cortical acto-myosin flow. The newly developed methods and established parameters will help in the characterization of known and the identification of novel regulators of IFP-containing aggregates.

| S-EPMC7840912 | biostudies-literature

SIRT6 facilitates directional telomere movement upon oxidative damage.

Project description:Oxidative damage to telomeres leads to telomere attrition and genomic instability, resulting in poor cell viability. Telomere dynamics contribute to the maintenance of telomere integrity; however, whether oxidative damage induces telomere movement and how telomere mobility is regulated remain poorly understood. Here, we show that oxidative damage at telomeres triggers directional telomere movement. The presence of the human Sir2 homolog, Sirtuin 6 (SIRT6) is required for oxidative damage-induced telomeric movement. SIRT6 knock out (KO) cells show neither damage-induced telomere movement nor chromatin decondensation at damaged telomeres; both are observed in wild type (WT) cells. A deacetylation mutant of SIRT6 increases damage-induced telomeric movement in SIRT6 KO cells as well as WT SIRT6. SIRT6 recruits the chromatin-remodeling protein SNF2H to damaged telomeres, which appears to promote chromatin decondensation independent of its deacetylase activity. Together, our results suggest that SIRT6 plays a role in the regulation of telomere movement upon oxidative damage, shedding new light onto the function of SIRT6 in telomere maintenance.

| S-EPMC5876328 | biostudies-literature

A cerebellar-thalamocortical pathway drives behavioral context-dependent movement initiation.

Project description:Executing learned motor behaviors often requires the transformation of sensory cues into patterns of motor commands that generate appropriately timed actions. The cerebellum and thalamus are two key areas involved in shaping cortical output and movement, but the contribution of a cerebellar-thalamocortical pathway to voluntary movement initiation remains poorly understood. Here, we investigated how an auditory "go cue" transforms thalamocortical activity patterns and how these changes relate to movement initiation. Population responses in dentate/interpositus-recipient regions of motor thalamus reflect a time-locked increase in activity immediately prior to movement initiation that is temporally uncoupled from the go cue, indicative of a fixed-latency feedforward motor timing signal. Blocking cerebellar or motor thalamic output suppresses movement initiation, while stimulation triggers movements in a behavioral context-dependent manner. Our findings show how cerebellar output, via the thalamus, shapes cortical activity patterns necessary for learned context-dependent movement initiation.

| S-EPMC8315304 | biostudies-literature

Directional Movement of Droplets in Grooves: Suspended or Immersed?

Project description:The behavior of droplets trapped in geometric structures is essential to droplet manipulation applications such as for droplet transport. Here we show that directional droplet movement can be realized by a V-shaped groove with the movement direction controlled by adjusting the surface wettability of the groove inner wall and the cross sectional angle of the groove. Experiments and analyses show that a droplet in a superhydrophobic groove translates from the immersed state to the suspended state as the cross sectional angle of the groove decreases and the suspended droplet departs from the groove bottom as the droplet volume increases. We also demonstrate that this simple grooved structure can be used to separate a water-oil mixture and generate droplets with the desired sizes. The structural effect actuated droplet movements provide a controllable droplet transport method which can be used in a wide range of droplet manipulation applications.

| S-EPMC4705533 | biostudies-literature

Collective directional movement and the perception of social cohesion.

Project description:We argue that perceivers associate collective directional movement - groups moving from one place to the next - with higher levels of social cohesion. Study 1 shows that pairs are rated as being more cohesive when described as engaging in directional movement compared to non-directional activities. Study 2 replicates this finding using film clips. Study 3 reveals that the proximity of directionally moving dyads is a better predictor of perceived cohesion than behavioural synchrony. Study 4 replicates the original finding and reveals that perceptions of common fate and shared goals both contribute to the effect, with the former having more predictive power than the latter. We suggest that collective directional movement is an invariant part of social environments and is utilized by perceivers to make inferences about social dynamics.

| S-EPMC7586976 | biostudies-literature

Lessons learned from UvrD helicase: mechanism for directional movement.

Project description:How do molecular motors convert chemical energy to mechanical work? Helicases and nucleic acids offer simple motor systems for extensive biochemical and biophysical analyses. Atomic resolution structures of UvrD-like helicases complexed with DNA in the presence of AMPPNP, ADP.Pi, and Pi reveal several salient points that aid our understanding of mechanochemical coupling. Each ATPase cycle causes two motor domains to rotationally close and open. At a minimum, two motor-track contact points of alternating tight and loose attachment convert domain rotations to unidirectional movement. A motor is poised for action only when fully in contact with its track and, if applicable, working against a load. The orientation of domain rotation relative to the track determines whether the movement is linear, spiral, or circular. Motors powered by ATPases likely deliver each power stroke in two parts, before and after ATP hydrolysis. Implications of these findings for analyzing hexameric helicase, F(1)F(0) ATPase, and kinesin are discussed.

| S-EPMC3480338 | biostudies-literature

Directional transport is mediated by a Dynein-dependent step in an RNA localization pathway.

Project description:Cytoplasmic RNA localization is a key biological strategy for establishing polarity in a variety of organisms and cell types. However, the mechanisms that control directionality during asymmetric RNA transport are not yet clear. To gain insight into this crucial process, we have analyzed the molecular machinery directing polarized transport of RNA to the vegetal cortex in Xenopus oocytes. Using a novel approach to measure directionality of mRNA transport in live oocytes, we observe discrete domains of unidirectional and bidirectional transport that are required for vegetal RNA transport. While kinesin-1 appears to promote bidirectional transport along a microtubule array with mixed polarity, dynein acts first to direct unidirectional transport of RNA towards the vegetal cortex. Thus, vegetal RNA transport occurs through a multistep pathway with a dynein-dependent directional cue. This provides a new framework for understanding the mechanistic basis of cell and developmental polarity.

| S-EPMC3640089 | biostudies-literature

MEKK2 and MEKK3 orchestrate multiple signals to regulate Hippo pathway.

Project description:The Hippo pathway is an evolutionarily conserved signaling pathway that controls organ size in animals via the regulation of cell proliferation and apoptosis. It consists of a kinase cascade, in which MST1/2 and MAP4Ks phosphorylate and activate LATS1/2, which in turn phosphorylate and inhibit YAP/TAZ activity. A variety of signals can modulate LATS1/2 kinase activity to regulate Hippo pathway. However, the full mechanistic details of kinase-mediated regulation of Hippo pathway signaling remain elusive. Here, we report that TNF activates LATS1/2 and inhibits YAP/TAZ activity through MEKK2/3. Furthermore, MEKK2/3 act in parallel to MST1/2 and MAP4Ks to regulate LATS1/2 and YAP/TAZ in response to various signals, such as serum and actin dynamics. Mechanistically, we show that MEKK2/3 interact with LATS1/2 and YAP/TAZ and phosphorylate them. In addition, Striatin-interacting phosphatase and kinase (STRIPAK) complex associates with MEKK3 via CCM2 and CCM3 to inactivate MEKK3 kinase activity. Upstream signals of Hippo pathway trigger the dissociation of MEKK3 from STRIPAK complex to release MEKK3 activity. Our work has uncovered a previous unrecognized regulation of Hippo pathway via MEKK2/3 and provides new insights into molecular mechanisms for the interplay between Hippo-YAP and NF-κB signaling and the pathogenesis of cerebral cavernous malformations.

| S-EPMC7948509 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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