Disease relevance of Cytoskeleton

• Epidermolysis bullosa simplex diseases demonstrate the function of the keratin cytoskeleton in resisting compaction stresses which otherwise lead to cell lysis [1].
• Putting E. coli on a pedestal: a unique system to study signal transduction and the actin cytoskeleton [2].
• Duchenne and Becker muscular dystrophies are caused by mutations in the gene encoding dystrophin, a component of the subsarcolemmal cytoskeleton [3].
• Third, drugs that disrupt the actin cytoskeleton, Cytochalasin D and and C2 Clostridium botulinum toxin induce a rapid block of [Ca2+]i rise, coincident with a block of the cyclic changes in T cell shape [4].
• Surprisingly, we find that ritonavir, but not indinavir, inhibits osteoclast differentiation in a reversible manner and also abrogates bone resorption by disrupting the osteoclast cytoskeleton, without affecting cell number [5].

Psychiatry related information on Cytoskeleton

• This is a controversial theory, however, primarily because there is a poor correlation between the concentrations and distribution of amyloid depositions in the brain and several parameters of AD pathology, including degree of dementia, loss of synapses, loss of neurons and abnormalities of the cytoskeleton [6].
• Isolation and chemical characterization of Alzheimer's disease paired helical filament cytoskeletons: differentiation from amyloid plaque core protein [7].
• The mechanism underlying cannibalism involved a complex framework, including lysosomal protease cathepsin B activity, caveolae formation, and ezrin cytoskeleton integrity and function [8].
• In support of this, there is good evidence that alterations in signaling pathways involving the Rho family of small GTPases, key regulators of the actin and microtubule cytoskeletons, contribute to both syndromic and nonsyndromic mental retardation disorders [9].

High impact information on Cytoskeleton

• All these receptors induce rearrangements in the actin cytoskeleton that lead to the internalization of the particle [10].
• Following the identification of WASP, the gene mutated in patients with this syndrome, and the more generally expressed WASP homologue N-WASP, studies have demonstrated that WASP-family molecules associate with numerous signaling molecules known to alter the actin cytoskeleton [11].
• We propose here a key role for PAK action in coordinating the dynamics of the actin and microtubule cytoskeletons during directional motility of cells, as well as in other functions requiring cytoskeletal polarization [12].
• In the absence of Cdc42 or Cdc24, the actin cytoskeleton does not become organized and budding does not take place [13].
• In addition, these macromolecular channel protein complexes appear to interact with the actin cytoskeleton and/or the extracellular matrix, suggesting important functional links between channel complexes, as well as between cardiac structure and electrical functioning [14].

Chemical compound and disease context of Cytoskeleton

• Rho, a small GTP-binding protein that regulates the actin cytoskeleton, is specifically antagonized by Clostridium botulinum C3 exoenzyme [15].
• The retinoic acid-induced differentiation of F-9 teratocarcinoma cells in monolayer culture is accompanied by the accumulation of fibrillar fibronectin deposits, the appearance of a highly structured actin cytoskeleton, and the redistribution of integrin to apparent sites of substrate contact [16].
• The epidermal growth factor receptor (EGF-R) on human epidermoid carcinoma cells, A431, was found to be predominantly associated with the detergent-insoluble cytoskeleton, where it retained both a functional ligand-binding domain and an intrinsic tyrosine kinase activity [17].
• Lymphoma Thy-1 glycoprotein is linked to the cytoskeleton via a 4.1-like protein [18].
• We have examined the effect of diphtheria toxin, Pseudomonas aeruginosa exotoxin A, and cycloheximide on the CV-1 cell cytoskeleton [19].

Biological context of Cytoskeleton

• We studied regulation of BB motility by analyzing myosin phosphorylation and its association with the cytoskeleton [20].
• Together, Mig-2, migfilin and filamin define a connection between cell matrix adhesions and the actin cytoskeleton and participate in the orchestration of actin assembly and cell shape modulation [21].
• Both phenotypes show similar blistering on trauma, indicating that both mutations compromise the structural resilience of the basal keratinocytes by affecting the keratin cytoskeleton [22].
• Brush border contraction occurs with ATP or with a mixture of ITP and ATP gamma S. Therefore, phosphorylation regulates myosin association with the cytoskeleton, myosin is not bound at the actin-myosin binding site, and when phosphorylated, myosin forms filaments for movement [20].
• Filamin A, encoded by the gene FLNA, is a widely expressed protein that regulates re-organization of the actin cytoskeleton by interacting with integrins, transmembrane receptor complexes and second messengers [23].

Anatomical context of Cytoskeleton

• Members of the armadillo protein gene family, which includes plakoglobin and beta-catenin, have important functions in cytoskeleton/cell membrane interactions [24].
• Rearrangement of the vimentin cytoskeleton during adipose conversion: formation of an intermediate filament cage around lipid globules [25].
• A 95,000 dalton actin-binding polypeptide, villin, has been purified to 98% homogeneity from brush border cytoskeletons of chicken intestinal epithelial cells [26].
• We have previously shown that treatment of T lymphocytes with mitogenic ligands induces a rapid activation of ornithine decarboxylase (ODC) through a mechanism that is independent of protein synthesis but requires energy and an intact cytoskeleton [27].
• Villin is a major protein of the microvillus cytoskeleton which binds both G and F actin in a calcium-dependent manner [28].

Associations of Cytoskeleton with chemical compounds

• Immunoprecipitation of Triton X-100-soluble and -insoluble cytoskeletal fractions with alpha- and beta-spectrin antisera show that, at steady state, alpha and beta spectrin are present in stoichiometric amounts, and exclusively, in the cytoskeleton [29].
• Are cells using stretch-activated ion channels to explore the extracellular environment surrounding them, or do they use for that purpose the submembrane protein network that interconnects integrin receptors with the actin cytoskeleton [30]?
• Ca(2+) signaling by calpains leads to controlled proteolysis during processes ranging from cytoskeleton remodeling in mammals to sex determination in nematodes [31].
• Role of phosphoinositide 3-OH kinase in cell transformation and control of the actin cytoskeleton by Ras [32].
• They also raise the possibility that PIP2 synthesis could mediate the effects of Rho on the actin cytoskeleton [33].

Gene context of Cytoskeleton

• Disruption of the single tropomyosin gene in yeast results in the disappearance of actin cables from the cytoskeleton [34].
• STS26T cells treated with NF2 antisense oligonucleotides showed alterations of the actin cytoskeleton [35].
• An important signaling pathway to the actin cytoskeleton links the Rho family GTPase Cdc42 to the actin-nucleating Arp2/3 complex through N-WASP [36].
• This novel protein, called CD2AP, is likely to facilitate receptor patterning in the contact area by linking specific adhesion receptors to the cytoskeleton [37].
• These data define a signaling pathway from Trio to Rac to Pak that links guidance receptors to the growth cone cytoskeleton [38].

Analytical, diagnostic and therapeutic context of Cytoskeleton

• Using immunofluorescence microscopy, we show that a truncated protein composed of the SH2 and SH3 domains of PLC-gamma was localized to the actin cytoskeleton [39].
• On the one hand, the determination of the structure of a bacterial actin-like protein MreB reveals the prokaryotic origins of the actin cytoskeleton, whereas on the other, cryo-electron microscopy and crystallography have yielded reconstructions of many actin crosslinking, regulatory and binding proteins in complex with F-actin [40].
• Rho GTPases hit the headlines several times in 1990-1992: the proteins regulating their GTP-GDP cycle were identified and they were found to be key signal transducers, mediating growth factor-induced changes to the actin cytoskeleton and activating the phagocyte NADPH oxidase [41].
• Laser scanning confocal microscopy was used to study the E7-induced modification of the endothelial cytoskeleton [42].
• Ligation of CR3 is sufficient to lead to Fc gamma RII association with the actin cytoskeleton on the adherent PMN surface [43].

References