Disease relevance of Intermediate Filaments

• The unique ability of the mesothelial cell to reversibly alter its morphology and intermediate filament composition is of unknown function and mechanism, but accounts for the morphological heterogeneity and the presence of keratin-negative cells in mesotheliomas [1].
• The pathological hallmark of all forms of Alexander disease is the presence of Rosenthal fibers, cytoplasmic inclusions in astrocytes that contain the intermediate filament protein GFAP in association with small heat-shock proteins [2].
• Histopathological features, including epithelial thickening, parakeratosis, extensive vacuolization of the suprabasal keratinocytes and compact aggregates of keratin intermediate filaments (KIF) in the upper spinous layers, resemble those found in epidermal disorders due to keratin defects [3].
• Specific interaction between HPV-16 E1-E4 and cytokeratins results in collapse of the epithelial cell intermediate filament network [4].
• Three cDNA clones of 1.6 (3u), 1.2 (5g) and 0.6 (5b) kbp, specific for peripherin, a neuronal intermediate filament protein (IFP), have been isolated from a murine neuroblastoma cell lambda gt11 library by immunoscreening using peripherin antiserum [5].

Psychiatry related information on Intermediate Filaments

• Familial cardiomyopathy, mental retardation and myopathy associated with desmin-type intermediate filaments [6].

High impact information on Intermediate Filaments

• Cotransfection of neurofilament light chain (NEFL) and mutant HSPB1 resulted in altered neurofilament assembly in cells devoid of cytoplasmic intermediate filaments [7].
• Among the myofibrillar proteins that characteristically accumulate within the muscle fibers of affected patients, the one found most consistently is desmin, a muscle-specific intermediate-filament protein responsible for the structural integrity of the myofibrils [8].
• Sensory neurodegeneration occurs in mice defective in BPAG1, a gene encoding cytoskeletal linker proteins capable of anchoring neuronal intermediate filaments to actin cytoskeleton [9].
• Missense mutations in the rod domain of the lamin A/C gene provide a genetic cause for dilated cardiomyopathy and indicate that this intermediate filament protein has an important role in cardiac conduction and contractility [10].
• The intermediate filament cytoskeleton of corneal epithelial cells is composed of cornea-specific keratins K3 and K12 (refs 1,2) [11].

Chemical compound and disease context of Intermediate Filaments

• Estrogen regulates the association of intermediate filament proteins with nuclear DNA in human breast cancer cells [12].
• These spheroids, which strikingly resemble the papillary structures in human mesotheliomas, are composed of mesothelial-like cells that produce hyaluronic acid and have a rich complement of intermediate filaments, predominantly cytokeratins [13].
• Two sublines of C6 rat glioma cells differing in their expression of the intermediate filament protein vimentin (vimentin expressing or vimentin negative cells) were stably transfected with a vector encoding tsp53 [14].
• We immunostained histologic sections of formalin-paraffin-processed specimens from 112 neuroendocrine tumors to evaluate the expression of intermediate filaments, especially neurofilament (NF) protein [15].
• We therefore undertook the present study to determine the relationships between glial and vimentin intermediate filaments (IFs), actin microfilaments, and CD44, a cell surface glycoprotein important in cell migration and invasion, in human astrocytoma cells [16].

Biological context of Intermediate Filaments

• Ultra-structural studies have identified abnormal keratin tonofilaments and linkage to the keratin gene cluster on chromosome 17 has been found in PC families [17].
• In metaphase to anaphase of normal mitosis and after colcemid arrest of mitotic stages, many cells contain all their detectable cytokeratin and vimentin material in the form of such spheroidal aggregate bodies, whereas in other mitotic cells such bodies occur simultaneously with bundles of residual intermediate filaments [18].
• Keratin 8 (mK8) and its partner keratin 18 (mK18) are the first intermediate filament proteins expressed during mouse embryogenesis [19].
• Disruption, by homologous recombination, of the gene encoding vimentin, a class III intermediate filament protein mainly expressed in vascular cells, was reported to result in apparently normal phenotype under physiological conditions [20].
• Abnormal expression of vimentin intermediate filaments in human lymphoid cell lines with deletion or translocation of the distal end of chromosome 8 [21].

Anatomical context of Intermediate Filaments

• Cultured cell Triton cytoskeletons enriched in intermediate filaments by extraction in high and low salt show, in addition to known intermediate-filament proteins and actin, a few other tenaciously bound polypeptides [22].
• We have assessed the mechanism of intermediate filament assembly by assaying the sites of incorporation of chicken vimentin subunits expressed under the control of an inducible promoter in transfected mouse fibroblasts [23].
• Expression vectors containing normal or mutant desmin cDNA were introduced into cultured cells to determine whether the mutant desmin formed intermediate filaments [8].
• The intermediate filament proteins, desmin and vimentin, are phosphorylated in skeletal muscle cells in vivo [24].
• It thus coexists in mature muscle fibers with desmin, the major subunit of muscle intermediate filaments [25].

Associations of Intermediate Filaments with chemical compounds

• Only trace amounts of phosphotyrosine were detected in myosin heavy chains, alpha-actinin, filamin, and the intermediate filament protein vimentin [26].
• We comment on the case of the epithelial integrin, alpha(6)beta(4), which may instead interact with intermediate filaments [27].
• Intermediate filaments and lipoprotein cholesterol [28].
• Based on the size, acidity, abundance, nonsolubilization by nonionic detergent and salt, and solubilization by urea, the hypothesis was advanced that the 58K-5.7 protein was the vimentin-type intermediate filament protein [29].
• Glial cells, identified by immunofluorescence analysis of their intermediate filaments, and a population of fibroblastlike cells were also present in retinoic acid-treated cultures of P19 cells [30].

Gene context of Intermediate Filaments

• These data imply that an intact keratin intermediate filament network is required for the maintenance of both cellular and tissue integrity [31].
• Keratins 1 (K1) and 10 (K10) are the predominant cytoskeletal intermediate filaments of epidermal cells during transition from the proliferative to the terminal differentiation stage [32].
• Glial fibrillary acidic protein (GFAP) is the main component of the intermediate filaments in cells of astroglial lineage, including astrocytes in the CNS, nonmyelin forming Schwann cells and enteric glia [33].
• Keratins 8 (K8) and 18 (K18) are major components of intermediate filaments (IFs) of simple epithelial cells and tumors derived from such cells [34].
• Desmoplakin (DPI), a desmosomal component lacking a transmembrane domain, has been implicated in this interaction, although most studies have been conducted with cells that contain few or no desmosomes, and efforts to demonstrate direct interactions between desmoplakin and intermediate filaments have not been successful [35].

Analytical, diagnostic and therapeutic context of Intermediate Filaments

• Western blotting using actin and neuronal intermediate filament preparations failed to show immunoreactivity with scleroderma sera containing antimyenteric neuronal antibodies [36].
• Electron microscopy demonstrated that alpha-crystallin particles could bind to intermediate filaments in a regular fashion, the spacing coinciding with the molecular length of GFAP [37].
• Two different antisera directed against the vimentin-containing intermediate filaments bind to polypeptides in the electrophoretic profiles of isolated HeLa and CHO cages and stain the cages, as visualized by indirect immunofluorescence [38].
• The p145 protein has the characteristics of an intermediate filament (IF) protein and immunoelectron microscopy shows that it colocalizes with vimentin, which suggests that these two proteins can coassemble into IFs [39].
• While studying intermediate filament assembly dynamics in the Xenopus oocyte, we used both VGS and size-exclusion chromatography (SEC) to analyze the soluble form of keratin [40].

References