• The microtubule cytoskeleton is critical for muscle cell differentiation and undergoes reorganisation into an array of paraxial microtubules, which serves as template for contractile sarcomere formation. (elifesciences.org)
  • Microtubules form the most rigid part of the cytoskeleton and are responsible for the intracellular movement of organelles or proteins. (ptglab.com)
  • One such protein is the cytoskeleton-associated protein 5 (CKAP5), widely expressed in a variety of cells to regulate the dynamics of microtubules in human cells. (medicalxpress.com)
  • In its GTP-bound form, Cdc42 binds several effectors that help direct polarized cell growth: repolarizing actin and microtubules, directing polarized exocytosis via this reoriented cytoskeleton and by direct contact with exocytic machinery, and recruiting proteins such as septins that form a boundary restricting the region of cell growth. (rupress.org)
  • Microtubules are polar cytoskeleton filaments that extend via growth at their plus ends. (uky.edu)
  • Kinetochores are protein complexes on the chromosomes, whose function as linkers between spindle microtubules and chromosomes is crucial for proper cell division. (nature.com)
  • In this study, we identify a previously uncharacterised isoform of microtubule-associated protein MAP4, oMAP4, as a microtubule organising factor that is crucial for myogenesis. (elifesciences.org)
  • The microtubules in cells that make smaller amounts of this protein were more disorganised, and these cells were unable to fuse with each other to form muscle cells. (elifesciences.org)
  • I also studied microtubule dynamics in living neurons transfected with GFP-tagged EB3, a protein binding specifically to polymerizing microtubule plus ends. (uni-muenchen.de)
  • The cytoskeletal network is composed of three different protein structures named filaments: microtubules, microfilaments (actin), and intermediate filaments. (ptglab.com)
  • The therapeutic potential of microtubule-associated protein targets for cancer therapy is a largely unexplored research area due to a lack of target-specific agents. (medicalxpress.com)
  • The protein is associated with microtubules , and Chatterjee and colleagues silenced the gene via short interfering RNA (siRNA) a molecular biological mechanism to study genes, targeting the CKAP5 encapsulated in lipid nanoparticles for in vivo delivery. (medicalxpress.com)
  • Several anterograde and retrograde signaling pathways, including the canonical Bone Morphogenic Protein (BMP) pathway , regulate synaptic development in vertebrates and invertebrates. (sdbonline.org)
  • We show here that an interaction of EB1 with the SXIP-containing +TIP CDK5 regulatory subunit-associated protein 2 (CDK5RAP2) regulates several EB1 activities, including microtubule plus-end tracking, dynamics at microtubule plus ends, microtubule and Ī±/Ī²-tubulin binding, and microtubule polymerization. (uky.edu)
  • An SXIP-binding-deficient EB1 mutant displayed significantly lower microtubule plus-end tracking than the wild-type protein in transfected cells. (uky.edu)
  • These results suggest that EB1 cooperates with CDK5RAP2 and perhaps other SXIPcontaining +TIPs in tracking growing microtubule tips.Wealso generated plus-end-tracking chimeras of CDK5RAP2 and the adenomatous polyposis coli protein (APC) and found that overexpression of the dimerization domains interfered with microtubule plus-end tracking of their respective SXIP-containing chimeras. (uky.edu)
  • A mutant protein makes the microtubules too stable to perform their jobs, the researchers find. (rupress.org)
  • One of these mutations leads to production of faulty dynamin 2, a protein that is crucial for endocytosis but also latches onto microtubules. (rupress.org)
  • Dynamin 2 also clings to microtubules of the mitotic spindle, and the team next wants to determine whether the protein regulates microtubule dynamics during the cell cycle. (rupress.org)
  • Kinesins are a protein superfamily that function via microtubules by converting energy released from ATP hydrolysis into mechanical work. (nottingham.ac.uk)
  • These pathways or roads are referred to as "microtubules", such as microscopic protein filaments. (expertmarketresearch.com)
  • The microtubule protein tubulin regulates adenylyl cyclase and phospholipase CĪ² 1 (PLCĪ² 1 ) signaling via transactivation of the G-protein subunits GĪ±s, GĪ±i1, and GĪ±q. (jneurosci.org)
  • Because most tubulin is not membrane associated, this study investigates whether tubulin translocates to the membrane in response to an agonist so that it might regulate G-protein signaling. (jneurosci.org)
  • It is suggested that G-protein-coupled receptors might modulate cytoskeletal dynamics, intracellular traffic, and cellular architecture. (jneurosci.org)
  • We also show that katanin reduces the levels of several types of post-translational modifications on tubulin of internal and cortical microtubules. (pasteur.fr)
  • Furthermore, katanin deficiencies phenocopy a mutation of beta-tubulin that prevents deposition of polymodifications (glutamylation and glycylation) on microtubules. (pasteur.fr)
  • Assessing posttranslational modifications of tubulin which serve as markers of microtubule turnover I found that microtubule stability is increased in a single neurite already before axon formation and in the axon of morphologically polarized cells. (uni-muenchen.de)
  • To study the effects of pharmaceutical compounds on the ratio of Tubulin to Microtubules in cells. (cytoskeleton.com)
  • To study the effects of mutated cell lines versus their parent cell line for the change in ratio of Tubulin to Microtubules. (cytoskeleton.com)
  • The most reproducible and accurate method of determining the amount of microtubule content versus free-tubulin content in a cell population is to use western blot quantitation of microtubule and free-tubulin cellular fractions. (cytoskeleton.com)
  • The general approach is to homogenize cells in microtubule stabilization buffer, followed by centrifugation to separate the microtubules from free-tubulin pool. (cytoskeleton.com)
  • Microtubules are 20 nm in diameter and are composed of alpha and beta tubulin subunits. (ptglab.com)
  • Post-translational modification of tubulin provides differential functions to microtubule networks. (xenbase.org)
  • This phenomenon of phase separation, at the microtubule level, increases the concentration of proteins, including tubulin, and significantly stimulates the growth rate of microtubules while reducing depolymerization events, i.e., microtubule decay events. (expertmarketresearch.com)
  • Essentially, these proteins separate from the cellular liquid to form a second liquid phase at the microtubule's tip, like oil droplets in water.This phase separation phenomenon significantly increases the concentration of certain proteins, including tubulin, which in turn, stimulate the growth rate of microtubules, while reducing their breakdown. (expertmarketresearch.com)
  • In SK-N-SH cells, carbachol induced a rapid and transient translocation of tubulin to the plasma membrane, microtubule reorganization, and a change in cell shape as demonstrated by confocal immunofluorescence microscopy. (jneurosci.org)
  • Pyr1 reversibly stabilizes microtubules, blocks actin microfilament dynamics and inhibits cell motility in vitro. (wikipedia.org)
  • When cofilin is phosphorylated, it regulates actin dynamics. (wikipedia.org)
  • In the presence of Pyr1, LIMK1 is inhibited, which means that the phosphorylation of cofilin decreases, which results in the blockage of the regulation of actin microfilaments dynamics and, therefore, the disorganization of microfilaments. (wikipedia.org)
  • In conclusion, Pyr1 inhibits cell motility and controls actin dynamics and stabilizes microtubules. (wikipedia.org)
  • Pyr1 may be used in cancer treatment, because its main target enzyme (LIM kinase) is a regulator of microtubule and actin dynamics. (wikipedia.org)
  • The Abl-related gene (Arg) requires its F-actin-microtubule cross-linking activity to regulate lamellipodial dynamics during fibroblast adhesion. (nih.gov)
  • Thus, intermediate filaments do not have as rigidly defined a structure as actin filaments or microtubules.Regardless of the composition, intermediate filaments have a diameter of around 10 nm. (ptglab.com)
  • These filaments are less dynamic and flexible than microtubules and actin filaments. (ptglab.com)
  • A family of microtubule-associated proteins (or 'MAPs' for short) bind to microtubules and assist in organising the filaments, but it is not clear how they work. (elifesciences.org)
  • The experiments also found that oMAP4 can create links between different microtubules and act as a brake to prevent the filaments being moved excessively by motor proteins. (elifesciences.org)
  • Cell mitosis is an attractive target to effectively treat a variety of cancer forms, where microtubule-associated proteins (MAPs) assist cells to maintain the stability of cell dynamics. (medicalxpress.com)
  • 183:1129-1143) provide new insights into how Cdc42 and Par proteins work together to modulate cell adhesion and polarity during embryonic morphogenesis by regulating the traffic of key cell junction proteins. (rupress.org)
  • Cdc42 interacts with proteins that regulate endocytosis and exocytosis and mediate traffic between ER and Golgi. (rupress.org)
  • Microtubule plus-end-tracking proteins (+TIPs) accumulate at these growing plus ends to control microtubule dynamics and attachment. (uky.edu)
  • According to the discovery by Julie Miesch, a Ph.D. student, and her team, two proteins, CLIP-170 and EB3, are responsible for controlling the growth of microtubules in cells through a unique liquid phase separation process. (expertmarketresearch.com)
  • It is observed that no communication is encountered between these proteins and microtubules when separated. (expertmarketresearch.com)
  • Additionally, how the teamwork of two proteins CLIP-170 and EB3 contributes massively to controlling the growth of microtubules by separating from the liquid within the cell and forming their own specialized liquid area. (expertmarketresearch.com)
  • This mechanism involves two specific proteins, CLIP-170 and EB3, undergoing a process called liquid-liquid phase separation at the tip of the microtubules during their growth. (expertmarketresearch.com)
  • CLIP-170 and EB3, when acting together, regulate the speed of microtubule growth at specific locations within the cell.The study used advanced microscopy techniques to observe the role of these two proteins both in vitro and in cellulo, providing insights into their functions.In conclusion, this discovery represents a significant advancement in understanding the regulation of microtubule dynamics within cells. (expertmarketresearch.com)
  • It also causes the stabilization of microtubules. (wikipedia.org)
  • One of them is to use molecules that can induce the stabilization of microtubules, and Pyr1 is one of them. (wikipedia.org)
  • By uncaging a photoactivatable analog of taxol I induced a local stabilization of microtubules at the neurite tip of an unpolarized neuron which was sufficient to favor the site of axon formation. (uni-muenchen.de)
  • This indicates that a transient stabilization of microtubules is sufficient to trigger axon formation. (uni-muenchen.de)
  • 2) Microtubule stabilization causes axon formation. (uni-muenchen.de)
  • 3) Microtubule stabilization precedes axon formation. (uni-muenchen.de)
  • I therefore deduce that microtubules are actively involved in the process of axon formation and that local microtubule stabilization in one neuronal process is a physiological signal specifying neuronal polarization. (uni-muenchen.de)
  • This polarized distribution of microtubule stability was confirmed by testing the resistance of neuronal microtubules to pharmacologically induced depolymerization. (uni-muenchen.de)
  • In my studies, I addressed the role of microtubule dynamics in initial neuronal polarization. (uni-muenchen.de)
  • To this end I aimed to investigate the following issues: 1) How do microtubule dynamics and stability change during initial neuronal development? (uni-muenchen.de)
  • Using hippocampal neurons in culture as a model system for neuronal polarization I first addressed the dynamics of microtubules in early developmental stages of neurons. (uni-muenchen.de)
  • By manipulating specific regulators of neuronal polarity, SAD kinases and GSK-3beta, I analyzed a possible relation between a polarization of microtubule stability and neuronal polarity. (uni-muenchen.de)
  • These results suggested that SAD kinases and GSK-3beta regulate neuronal polarization -at least in part- by modulating microtubule dynamics. (uni-muenchen.de)
  • To establish a possible causal relation between microtubule dynamics and axon formation I assessed the effects of specific pharmacological alterations of microtubule dynamics on neuronal polarization. (uni-muenchen.de)
  • In summary, my data allow the following conclusions: 1) Microtubule stability correlates with the identity of a neuronal process. (uni-muenchen.de)
  • I found that a loss of polarity correlated with a loss of polarized microtubule stability in neurons defective for SAD A and SAD B kinases. (uni-muenchen.de)
  • Together with dynactin, dynein regulates centrosomal orientation to establish and maintain cell polarity, controls focal adhesion turnover and anchors microtubules at the leading edge. (biologists.com)
  • Cdc42 also affects other aspects of cell polarity, including microtubule dynamics, centrosome positioning, and Golgi reorientation. (rupress.org)
  • Here, we report that AQP5 promotes microtubule assembly and helps maintain the assembled microtubule steady state levels with slower turnover dynamics in cells . (plos.org)
  • The researchers also found that blocking normal dynamin 2 with RNAi had the same effect as the mutation, confirming that one of dynamin 2's functions is to promote microtubule turnover. (rupress.org)
  • Within the myoblasts, long filaments called microtubules are arranged in an overlapping linear pattern. (elifesciences.org)
  • used microscopy to observe the formation of the microtubule filaments in living myoblasts. (elifesciences.org)
  • The in vivo significance of microtubule severing and the mechanisms governing its spatial regulation are not well understood. (pasteur.fr)
  • Regulation of MT dynamics via direct binding of an Abl family kinase. (nih.gov)
  • These findings indicate that AQP5-mediated regulation of microtubule dynamics modulates airway epithelial barrier properties and epithelial function. (plos.org)
  • This suggests that Kinesin-13Cs do not function in microtubule regulation. (nottingham.ac.uk)
  • The researchers screened 20 solid cancer cell lines relative to gene silencing to identify a highly responsive chemo-resistant ovarian cancer cell line that underwent significant depletion in mitotic spindle-dynamics for effective experimental cancer treatment. (medicalxpress.com)
  • Kin13-1 cleaving activity has revealed a possible means of regulating the mitotic spindle, and thus chromosome segregation, which was previously unidentified. (nottingham.ac.uk)
  • Ciliary development and maintenance depend critically on a specific, microtubule-based intracellular transport mechanism, intraflagellar transport (IFT). (europa.eu)
  • In contrast, overexpression of AQP5 increased assembly of microtubules, with evidence of increased MT stability, and promoted the formation of long straight microtubules in the apical domain of the epithelial cells. (plos.org)
  • The axon of polarized neurons and a single neurite in morphologically unpolarized cells showed increased microtubule stability. (uni-muenchen.de)
  • Thus, I established a correlation between the identity of a process and its microtubule stability. (uni-muenchen.de)
  • In marked contrast, the formation of multiple axons, induced by the inhibition of GSK-3beta, was associated with increased microtubule stability in these supernumerary axons. (uni-muenchen.de)
  • In Tetrahymena, a cell type with elaborate microtubule arrays, we engineered null mutations in subunits of the microtubule-severing complex, katanin. (pasteur.fr)
  • Moreover, it has been shown that Pyr1 is toxic for cancerous cell lines, even the ones that are resistant to conventional microtubule targeting agents. (wikipedia.org)
  • In order to distribute the genetic material equally, the cell forms a spindle, a precise micro-machine made of microtubules (MTs) to which all chromosomes have to be correctly targeted. (nature.com)
  • Dynamic changes in airway epithelial paracellular permeability allow for receptor-ligand access across the airway epithelium, and thereby regulate cell signaling [11] . (plos.org)
  • Therefore, the next challenge is to understand how other processes-such as the selective stabilisation of some microtubules and the movement of cell materials along the microtubules-cooperate to control muscle fibre formation. (elifesciences.org)
  • dGLYAT was found to regulate Gadd45 -mediated JNK pathway activation and cell invasion. (sdbonline.org)
  • There are opposing forces that regulate intercalation, namely, the restrictive forces of the epithelial barrier versus the penetrative forces of the intercalating cell. (xenbase.org)
  • It is a necessity of cell division and plays a role by regulating microtubule dynamics and chromosome aggregation [ 12 ]. (aging-us.com)
  • This study has helped several other research enthusiasts to get a better understanding of how things work inside a human cell focusing on microtubules. (expertmarketresearch.com)
  • In higher eukaryotes, dynein/dynactin requires additional components such as Bicaudal D to form an active motor complex and for regulating its cellular localization. (biologists.com)
  • It is observed that the behaviour of cellular microtubules is directly and physically impacted by this mechanism. (expertmarketresearch.com)
  • This newly discovered mechanism appears to play a concrete role in controlling the dynamics of cellular microtubules.The synergy between CLIP-170 and EB3 is crucial for regulating microtubule growth, owing to this phase separation mechanism. (expertmarketresearch.com)
  • Purified oMAP4 aligns dynamic microtubules into antiparallel bundles that withstand motor forces in vitro. (elifesciences.org)
  • To characterise KIF12-microtubule interactions in vitro, the human RefSeq reference standard KIF12 (rsKif12) sequence was used. (nottingham.ac.uk)
  • T. brucei Kinesin-13s Kin13-1, -3 (both 13A) and -6 (13C) interactions with microtubules were observed in vitro. (nottingham.ac.uk)
  • Kin13-6 does not significantly change microtubule dynamics in vitro. (nottingham.ac.uk)
  • Cilia consist of an axoneme built of microtubules, enveloped by a specialized membrane. (europa.eu)
  • In addition, it separates and regulates access between the apical and basolateral membrane domains of polarized epithelia. (plos.org)
  • Importantly, Cdc42 regulates membrane traffic at numerous sites. (rupress.org)
  • Airway epithelial cells can dynamically regulate paracellular permeability in response to both physiologic and pathologic stimuli [6] , [11] . (plos.org)
  • AQP5 can regulate paracellular permeability in primary airway epithelial cells [6] . (plos.org)
  • Most notably, oMAP4 is required for paraxial microtubule organisation in muscle cells and prevents dynein- and kinesin-driven microtubule-microtubule sliding. (elifesciences.org)
  • But microtubules from cells that made the faulty version of dynamin 2 were abnormally stable, as measured by how many acetyl groups were attached to them. (rupress.org)
  • This was studied in SK-N-SH neuroblastoma cells, which possess a muscarinic receptor-regulated PLCĪ² 1 -signaling pathway. (jneurosci.org)
  • These interactions or localization of the complex may be regulated by Cdc42. (rupress.org)
  • In line with my previous observations I found that microtubules are stabilized along the shaft of the growing axons while dynamic microtubules enrich at the tip of the growing process, suggesting that a well- balanced shift of microtubule dynamics towards more stable microtubules is necessary to induce axon formation. (uni-muenchen.de)
  • The SXIP motif fused with a dimerization domain from CDK5RAP2 significantly enhanced EB1 plus-end-tracking and microtubule-polymerizing and bundling activities, but the SXIP motif alone failed to do so. (uky.edu)
  • We propose a model in which the cooperation of dynein-mediated microtubule transport and oMAP4-mediated zippering of microtubules drives formation of a paraxial microtubule array that provides critical support for the polarisation and elongation of myotubes. (elifesciences.org)
  • Dynein is the sole processive minus-end-directed microtubule motor found in animals. (biologists.com)
  • Charlotte Aumeier, the study's last author, explains, "Microtubules are dynamic structures that continually build and deconstruct themselves. (expertmarketresearch.com)
  • The mechanisms that facilitate kinetochore capture by microtubules are still unclear. (nature.com)
  • A major +TIP class contains the SXIP (Ser-X-Ile-Pro, with X denoting any amino acid residue) motif, known to interact with EB1 and its homologs for plus-end tracking, but the role of SXIP in regulating EB1 activities is unclear. (uky.edu)
  • The family of tyrosine-kinase receptors, including those for epithelial growth factor (EGFR) and the transporter for the neurotransmitter dopamine (DAT), are regulated in this way. (alzforum.org)
  • [6] . Others have shown a similar change in paracellular permeability regulated by AQP5 in salivary glands, however in that system it was associated with alterations in claudin-7, claudin-3, and occludin [5] . (plos.org)
  • As in a petrochemical plant, different steps in the production process take place in dedicated compartments, and signaling systems regulate the movement of molecules between compartments. (alzforum.org)
  • In addition to regulating transcellular water permeability, AQP5 can regulate paracellular permeability, though the mechanisms by which this occurs have not been determined. (plos.org)
  • This groundbreaking study has undoubtedly paved the way toward innovative treatments aimed at combating the devastating effects of cancer and degenerative diseases.The key finding of this research involves the identification of a new mechanism governing the growth of microtubules. (expertmarketresearch.com)
  • Studying and learning about the functioning process of these microtubules, including control over their own growth, is significant, even though it is a progressive area but still sophisticated, requiring more research work. (expertmarketresearch.com)
  • However, the growth of the microtubule can be controlled by them when coupled with each other. (expertmarketresearch.com)
  • These experiments will place my lab in a unique position to push forward our understanding of the relationship between structure, function and dynamics of transport of this fascinating and fundamental organelle. (europa.eu)
  • Instead, the experiments suggest that Tao negatively regulates BMP signaling as reduction of Tao leads to an increase in pMad levels in motor neuron nuclei and an increase in BMP target gene expression. (sdbonline.org)
  • The latest study by some researchers from the University of Geneva exhibit that these microtubules could possibly grow and function by techniques that are unfamiliar so far. (expertmarketresearch.com)
  • Our results suggest that disruption of SXIP dimerization enables detailed investigations of microtubule plus-endassociated functions of individual SXIP-containing +TIPs. (uky.edu)
  • Kin13-3 depolymerises microtubules, consistent with the functions of other Kinesin-13A members. (nottingham.ac.uk)
  • 3) What are possible regulators mediating changes in microtubule dynamics during axon formation? (uni-muenchen.de)
  • Conversely, low doses of the microtubule stabilizing drug taxol led to the formation of multiple axons. (uni-muenchen.de)
  • The dynamics of RACK1 levels in isolated adult SC of mice, i.e., progressively high during differentiation and low compared to proliferating conditions, and RACK1 silencing indicated that RACK1 promotes both the formation of myotubes and the accretion of nascent myotubes. (sdbonline.org)