Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Potential interactors of alpha-tubulin acetyltransferase 1 (αTAT1/MEC17)

ABSTRACT: Cell adhesion to the extracellular matrix occurs through integrin-mediated focal adhesions, which sense the mechanical properties of the substrate and impact cellular functions such as cell migration. Mechanotransduction at focal adhesions affects the actomyosin network and contributes to cell migration. Despite being key players in cell adhesion and migration, the role of microtubules in mechanotransduction has been overlooked. Here, we show that substrate rigidity increases microtubule acetylation through β1 integrin signalling in primary rat astrocytes. Moreover, αTAT1, the enzyme responsible for microtubule acetylation, interacts with a major mechanosensing focal adhesion protein, Talin, and is able to tune the distribution of focal adhesions depending on the matrix rigidity. αTAT1 also reorganises the actomyosin network, increases traction force generation and cell migration speed on stiff substrates. Mechanistically, acetylation of microtubules promotes the release of microtubule-associated RhoGEF, GEF-H1 into the cytoplasm, which then leads to RhoA activation and high actomyosin contractility. Thus, we propose a novel feedback loop involving a crosstalk between microtubules and actin in mechanotransduction at focal adhesions whereby, cells sense the rigidity of the substrate through integrin-mediated adhesions, modulate their levels of microtubule acetylation, which then controls the actomyosin cytoskeleton and force transmission on the substrate to promote mechanosensitive cell migration.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hek-293 Cell

SUBMITTER: Valentin SABATET

LAB HEAD: Damarys Loew

PROVIDER: PXD015871 | Pride | 2021-11-02

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Similar Datasets

Fibroblast-tracks are topographical cues that direct cancer cell migration

Project description:Fibroblasts rely on adhesive structures to migrate. It is generally thought that adhesive structures disassemble once at the rear of the cell to release the cell and allow further movement. However, a significant portion of adhesions is not disassembled and is instead left on the substrate. We observed that virtually all the non-resorbed adhesions remain connected to the substrate by the means of integrin β5. Forward cell migration results in plasma membrane pulling giving rise to tubular structures that are then left on the ground, forming a network of lipid tracks that persist for several days, thus altering substrate’s topography. Cancer cells of different origin exploit fibroblast-tracks as migration railways. The adhesion of cancer cells along tracks is not mediated by focal adhesions, but rather by frustrated clathrin-coated structures (CCSs). Analysis of the composition of track generated by cancer associated fibroblasts allowed to identify integrin αv as the receptor on cancer cells responsible for track recognition. Some cancer cell lines are not able to perform durotaxis (rigidity driven migration), while fibroblasts are very good at it. We thus tested whether, in the presence of fibroblast-tracks, non-durotactic cancer cells would become durotactic by following tracks and this was indeed the case. Hence, fibroblast-tracks are a novel structure capable of physically directing cell migration of different cell types.

2023-09-22 | PXD034091 | Pride

Mechanical Regulation of Stem Cell Proliferation and Fate Decisions by their Differentiated Daughters

Project description:RNAseq analysis of suprabasal cells in the epidermis of control and K10rtTA;TRESpastin (which depolymerize microtubules) at E16.5 were performed. We observed the premature differentiation of the barrier and increased actomyosin contractility in suprabasal differentiated cells upon microtubule disruption compared to control, and proved the increased actomyosin contractility caused by microtubule depolymerization leads to basal stem cell hyperproliferation during epidermal development.

2020-12-01 | GSE158785 | GEO

Transcriptional regulation of cellular mechanosignaling by PREP1 (PKNOX1)

Project description:Mechanosignaling, initiated by the extracellular physical forces and propagated through the intracellular cytoskeletal network, triggers signaling cascades leading to processes such as embryogenesis, tissue maintenance and disease development. While signal transduction by transcription factors occurs downstream of cellular mechanosensing, nothing is known about the cell intrinsic mechanisms that can regulate mechanosignaling. Here we show that transcription factor PREP1 (PKNOX1) regulates the expression of LINC complex proteins and mechanotransduction of YAP-TAZ. PREP1 depletion upsets the nuclear membrane protein stoichiometry rendering nuclei soft. However, reduced nuclear tension is not conveyed to the cytoplasm, since these cells display fortified actomyosin network with bigger focal adhesion complexes resulting in greater traction forces at the substratum. Intriguingly, YAP-TAZ remains localized to the cytoplasm irrespective of the substrate rigidity indicating disrupted mechanotransduction. Our data demonstrate a hitherto unknown transcriptional mechanism which regulate mechanosignaling upstream of YAP-TAZ transduction.

2022-03-14 | GSE160286 | GEO

Matrix rigidity and cardiac reprogramming

Project description:Direct cardiac reprogramming from fibroblasts holds great potential for disease modeling, drug screening, and regeneration. However, cardiac reprogramming remains inefficient in vitro, and induced cardiomyocytes (iCMs) generated in vitro are less mature than those in vivo, suggesting undefined biophysical factors may inhibit cardiac reprogramming. Previous studies mainly used conventional polystyrene dishes, and thus the effect of matrix rigidity on cardiac reprogramming remains unclear. Here, we developed a Matrigel-based hydrogel culture system to determine the effect of matrix rigidity and mechanotransduction on cardiac reprogramming. We found that soft matrix rigidity comparable to myocardium greatly enhanced cardiac reprogramming in combination with Gata4, Hand2, Mef2c, and Tbx5. Mechanistically, soft matrix enhanced cardiac reprogramming via inhibition of Rho/ROCK, actomyosin, and YAP/TAZ pathway, and suppression of fibroblast program, which were activated on rigid substrate. Intriguingly, inhibition of YAP/TAZ further suppressed integrin-mediated signaling to create a positive feedback loop for robust reprogramming. Thus, mechanotransduction may represent a new target for cardiac reprogramming.

2020-08-28 | GSE125811 | GEO

CCM3 is a gatekeeper in focal adhesions regulating mechanotransduction and YAP/TAZ signalling

Project description:CCM3 is a gatekeeper in focal adhesions regulating mechanotransduction and YAP/TAZ signalling

| PRJNA655226 | ENA

Microtubule acetylation is required for mechanosensation in Drosophila

Project description:At the cellular level, α-tubulin acetylation alters the structure of microtubules to render them mechanically resistant to compressive forces. How this biochemical property of microtubule acetylation relates to mechanosensation remains unknown, though prior studies have shown that microtubule acetylation influences touch perception. Here, we identify the major Drosophila α-tubulin acetylase (dTAT) and show that it plays key roles in several forms of mechanosensation. dTAT is highly expressed in the larval peripheral nervous system (PNS), but is largely dispensable for neuronal morphogenesis. Mutation of the acetylase gene or the K40 acetylation site in α-tubulin impairs mechanical sensitivity in sensory neurons and behavioral responses to gentle touch, harsh touch, gravity, and vibration stimuli, but not noxious thermal stimulus. Finally, we show that dTAT is required for mechanically-induced activation of NOMPC, a microtubule-associated transient receptor potential channel, and functions to maintain integrity of the microtubule cytoskeleton in response to mechanical stimulation.

2018-09-22 | GSE120305 | GEO

Gene expression profiling of Tsp1 deficient rat aortic smooth muscle cells with mechanical stretch

Project description:The extracellular matrix (ECM) initiates mechanical cues and transduces intracellular signaling through matrix-cell interactions. The nature of cues and how they coordinate with a mechanical microenvironment are not fully understood. We identified the matricellular protein, thrombospondin-1 (Tsp1, also called Thbs1), as a mediator of matrix mechanotransduction that acts via integrin αvβ1 to establish focal adhesions and promotes nuclear shuttling of Yes-associated protein (YAP) in response to cyclic stretch. Thbs1-mediated YAP activation depends on the small GTPase Rap2 and Hippo pathway, and is not influenced by altered actin fibers. Hence, to gain insight into the molecular mechanisms underlying the Tsp1-mediated matrix mechanotransduction, we performed a comprehensive analysis of gene expression changes in Tsp1deficiant SMCs with mechanical stretch using RNA sequencing (RNA-Seq).

2020-03-17 | GSE131750 | GEO

Ambra1 spatially regulates Src activity and Src/FAK-mediated cancer cell invasion via trafficking networks

Project description:Here, using mouse squamous cell carcinoma cells, we report a completely new function for the autophagy protein Ambra1 as the first described ‘spatial rheostat’ controlling the Src/FAK pathway. Ambra1 regulates the targeting of active phospho-Src away from focal adhesions into autophagic structures that cancer cells use to survive adhesion stress. Ambra1 binds to both FAK and Src in cancer cells. When FAK is present, Ambra1 is recruited to focal adhesions, promoting FAK-regulated cancer cell direction-sensing and invasion. However, when Ambra1 cannot bind to FAK, abnormally high levels of phospho-Src and phospho-FAK accumulate at focal adhesions, positively regulating adhesion and invasive migration. Spatial control of active Src requires the trafficking proteins Dynactin 1 and IFITM3, which we identified as Ambra1 binding partners by interaction proteomics. We conclude that Ambra1 is a core component of an intracellular trafficking network linked to tight spatial control of active Src and FAK levels, and so crucially regulates their cancer-associated biological outputs.

2017-04-04 | PXD006002 | Pride

Influence of substrate stiffness on the proteome of undifferentiated human umbilical cord matrix mesenchymal stem/stromal cells (hUCM-MSCs)

Project description:Cells sense the biophysical properties of the surrounding microenvironment. In particular, the stiffness of the extracellular milieu can be interrogated by cells and integrated through mechanotransduction. Many cellular processes (like proliferation, migration, or differentiation) depend on the mechanical status of the cell (being largely dictated by actomyosin-dependent intracellular contractility), which in turn is influenced by the mechanical properties of the microenvironment. In this study, we explored the influence of substrate stiffness on the proteome of undifferentiated human umbilical cord matrix mesenchymal stem/stromal cells (hUCM-MSCs). The relative abundance of several identified proteins suffered significant changes when comparing between substrates. Interestingly, many of such proteins are related to the regulation of the actin cytoskeleton, a main player of mechanotransduction and cell physiology in response to mechanical cues.

2020-07-20 | PXD017674 | Pride

Transcription Level Response of HEK-293T Cells to RfA1 Expression

Project description:We transfected HEK-293T cells to express RfA1. The RNA-Seq results indicates that Genes evolved in biological processes such as “regulation of microtubule cytoskeleton organization”, “microtubule polymerization or depolymerization”, “microtubule nucleation” were found to respond to RfA1 expression. Correspondingly, these microtubule relevant genes were also sorted to cellular component items, including “spindle microtubule”, “spindle pole centrosome”, “mitotic spindle”, “spindle” , which indicates the tight relationship between RfA1 and microtubules.

2021-11-01 | GSE186861 | GEO

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