Search results for "cytoskeleton"
showing 10 items of 272 documents
Specific release of membrane-bound annexin II and cortical cytoskeletal elements by sequestration of membrane cholesterol
1997
Annexin II is an abundant protein which is present in the cytosol and on the cytoplasmic face of plasma membrane and early endosomes. It is generally believed that this association occurs via Ca(2+)-dependent binding to lipids, a mechanism typical for the annexin protein family. Although previous studies have shown that annexin II is involved in early endosome dynamics and organization, the precise biological role of the protein is unknown. In this study, we found that approximately 50% of the total cellular annexin was associated with membranes in a Ca(2+)-independent manner. This binding was extremely tight, since it resisted high salt and, to some extent, high pH treatments. We found, h…
Patterns of Expression and Organization of Cytokeratin Intermediate Filaments
1985
Cytokeratins are a large multigene family comprising two polypeptide types, i.e. acidic (type I) and basic (type II) ones, which are distinguished on the basis of immunological, peptide mapping, mRNA hybridization, and primary amino acid sequence data. The acidic (type I) cytokeratins can be subdivided into at least two different subtypes on the basis of their carboxy-terminal sequences. Considerable interspecies conservation of sequences exists, even extending to the 3'-non-coding mRNA regions. Different pairs of type I and II cytokeratins show different resistance to dissociation in urea. Sequence differences of the type I cytokeratins containing functional domains may be an explanation o…
Factors Determining Sensitivity and Resistance of Tumor Cells to Arsenic Trioxide
2012
Previously, arsenic trioxide showed impressive regression rates of acute promyelocytic leukemia. Here, we investigated molecular determinants of sensitivity and resistance of cell lines of different tumor types towards arsenic trioxide. Arsenic trioxide was the most cytotoxic compound among 8 arsenicals investigated in the NCI cell line panel. We correlated transcriptome-wide microarray-based mRNA expression to the IC(50) values for arsenic trioxide by bioinformatic approaches (COMPARE and hierarchical cluster analyses, Ingenuity signaling pathway analysis). Among the identified pathways were signaling routes for p53, integrin-linked kinase, and actin cytoskeleton. Genes from these pathways…
Tension Causes Unfolding of Intracellular Vimentin Intermediate Filaments
2020
Intermediate filament (IF) proteins are a class of proteins that constitute different filamentous structures in mammalian cells. As such, IF proteins are part of the load-bearing cytoskeleton and support the nuclear envelope. Molecular dynamics simulations show that IF proteins undergo secondary structural changes to compensate mechanical loads, which is confirmed by experimental in vitro studies on IF hydrogels. However, the structural response of intracellular IF to mechanical load is yet to be elucidated in cellulo. Here, in situ nonlinear Raman imaging combined with multivariate data analysis is used to quantify the intracellular secondary structure of the IF cytoskeletal protein viment…
Lack of GDAP1 induces neuronal calcium and mitochondrial defects in a knockout mouse model of Charcot-Marie-tooth neuropathy
2015
27 páginas, 9 figuras.
Fractal-related assembly of the axial filament in the demosponge Suberites domuncula: relevance to biomineralization and the formation of biogenic si…
2007
Abstract The siliceous spicules of sponges (Porifera) show great variations of sizes, shapes and forms; they constitute the chief supporting framework of these animals; these skeletal elements are synthesized enzymatically by silicatein. Each sponge species synthesizes at least two silicateins, which are termed − α and − β . In the present study, using the demosponge Suberites domuncula , we studied if the silicateins of the axial filament contribute to the shape formation of the spicules. For these experiments native silicateins have been isolated by a new Tris/glycerol extraction procedure. Silicateins isolated by this procedure are monomeric (24 kDa), but readily form dimers through non-…
Flexible Structure of Peptide-Bound Filamin A Mechanosensor Domain Pair 20-21.
2015
Filamins (FLNs) are large, multidomain actin cross-linking proteins with diverse functions. Besides regulating the actin cytoskeleton, they serve as important links between the extracellular matrix and the cytoskeleton by binding cell surface receptors, functioning as scaffolds for signaling proteins, and binding several other cytoskeletal proteins that regulate cell adhesion dynamics. Structurally, FLNs are formed of an amino terminal actin-binding domain followed by 24 immunoglobulin-like domains (IgFLNs). Recent studies have demonstrated that myosin-mediated contractile forces can reveal hidden protein binding sites in the domain pairs IgFLNa18-19 and 20-21, enabling FLNs to transduce me…
Assembly of a Filamin Four-domain Fragment and the Influence of Splicing Variant-1 on the Structure
2011
Filamins are scaffold proteins that bind to various proteins, including the actin cytoskeleton, integrin adhesion receptors, and adaptor proteins such as migfilin. Alternative splicing of filamin, largely constructed from 24 Ig-like domains, is thought to have a role in regulating its interactions with other proteins. The filamin A splice variant-1 (FLNa var-1) lacks 41 amino acids, including the last β-strand of domain 19, FLNa(19), and the first β-strand of FLNa(20) that was previously shown to mask a key binding site on FLNa(21). Here, we present a structural characterization of domains 18-21, FLNa(18-21), in the FLNa var-1 as well as its nonspliced counterpart. A model of nonspliced FLN…
Structural basis of the migfilin-filamin interaction and competition with integrin beta tails.
2008
A link between sites of cell adhesion and the cytoskeleton is essential for regulation of cell shape, motility, and signaling. Migfilin is a recently identified adaptor protein that localizes at cell-cell and cell-extracellular matrix adhesion sites, where it is thought to provide a link to the cytoskeleton by interacting with the actin cross-linking protein filamin. Here we have used x-ray crystallography, NMR spectroscopy, and protein-protein interaction studies to investigate the molecular basis of migfilin binding to filamin. We report that the N-terminal portion of migfilin can bind all three human filamins (FLNa, -b, or -c) and that there are multiple migfilin-binding sites in FLNa. H…
Structure of three tandem filamin domains reveals auto-inhibition of ligand binding
2007
Human filamins are large actin-crosslinking proteins composed of an N-terminal actin-binding domain followed by 24 Ig-like domains (IgFLNs), which interact with numerous transmembrane receptors and cytosolic signaling proteins. Here we report the 2.5 A resolution structure of a three-domain fragment of human filamin A (IgFLNa19-21). The structure reveals an unexpected domain arrangement, with IgFLNa20 partially unfolded bringing IgFLNa21 into close proximity to IgFLNa19. Notably the N-terminus of IgFLNa20 forms a beta-strand that associates with the CD face of IgFLNa21 and occupies the binding site for integrin adhesion receptors. Disruption of this IgFLNa20-IgFLNa21 interaction enhances fi…