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PubMedDate not supplied

The distribution of intermediate filament proteins, actin and desmoplakins in human placental tissue as revealed by polyclonal and monoclonal antibodies.

The distribution of intermediate filament proteins (cytokeratin, vimentin, desmin), actin, and desmoplakins in various placental compartments was studied by immunofluorescence microscopy using polyclonal and monoclonal antibodies. Trophoblast cells (cytotrophoblast, syncytiotrophoblast, isolated trophoblast cells, trophoblastic giant cells) were strongly stained by all types of cytokeratin antibodies. Antibodies to desmoplakins revealed the presence of desmosomes at all membranes, except the basal membrane of cytotrophoblast cells, and at the basal as well as the lumen-oriented membrane of the syncytiotrophoblast. After disappearance of the cytotrophoblast cell layer the distribution of desmosomes in the syncytiotrophoblast was unaltered. Isolated trophoblast cells contained desmosomes around their entire circumference. Amnion epithelial cells were heterogeneous with respect to cytokeratin composition as revealed, for example, by polyclonal antibodies with a broad range of cytokeratin reactivity and by monoclonal antibodies to cytokeratin No. 18. With the latter, a heterogeneous staining of amnion epithelial cells was achieved. Desmosomes (spots reactive with desmoplakin antibodies) were present at the lateral membranes of the amnion epithelial cells. In addition, vimentin filaments were coexpressed in these cells. Large vessels of the chorionic plate and stem villi showed thick walls consisting of vimentin-, desmin- and actin-positive cells. They were surrounded by mantles rich in vimentin-, desmin- and actin-positive cells, resembling myofibroblasts. This indicates that these cells may play a role in villous contractility and modulation of the intervillous space with effect on both maternal and fetal placental circulation.

Actins↗
PubMed2004

Intermediate filament steady-state mRNA levels in amyotrophic lateral sclerosis.

We have examined the steady-state levels of intermediate filament mRNA in amyotrophic lateral sclerosis using the RNAse protection assay (NFL, NFM, NFH; corrected against GAPDH) or by PCR (peripherin, alpha-internexin, nestin, and vimentin; corrected against beta-actin). Significant elevations of NFL and peripherin mRNA levels were observed within the ALS cervical and lumbar spinal cord, with all other IF mRNA levels being comparable between control and ALS cases. These findings suggest that disturbances in both NFL and peripherin expression, independently known to contribute to the generation of motor neuron dysfunction in transgenic mice, are evident in ALS.

Amyotrophic Lateral Sclerosis↗
PubMed1994

Giant axonal neuropathy: a generalized disorder of intermediate filaments with longitudinal grooves in the hair.

Giant axonal neuropathy (GAN) is a generalized neurological disorder with accumulation of intermediate filaments in different cell populations. The hallmark are enormous axonal swellings containing densely packed neurofilaments. Clinical symptoms reported so far are mainly limited to the nervous system. We report on a four-year-old girl with clinical and sural nerve biopsy findings typical of GAN. In addition, scanning electron microscopy (SEM) showed longitudinal grooves in the hairs of our patient. This peculiarity so far has only been described in two other patients with GAN. Scanning electron microscopy of hairs therefore may serve as a method of screening in patients suspected of suffering from GAN.

Axons↗
PubMed1990

Organization of intermediate filaments and their association with collagen-containing phagosomes in mouse decidual cells.

We have analyzed the distribution of intermediate filaments (IF) in the cytoplasm of mature decidual cells of mice. IF were scattered throughout the cytoplasm of these cells although there was a preferential accumulation around the nuclei. In many cells a large area of the cytoplasm was occupied by a rich network of IF that extended from the perinuclear region toward the cell surface. Thin bundles of IF crossed the cytoplasm without a preferential orientation. IF were also seen in close association with nuclear pore complexes, gap junctions, mitochondria, and lysosomes. A very developed network of IF surrounded phagosomes that contained collagen fibrils. Longitudinal and cross sections of these phagosomes showed a very close association of IF with the phagosome membrane.

Animals↗
PubMed1983

Amino acid sequence data on glial fibrillary acidic protein (GFA); implications for the subdivision of intermediate filaments into epithelial and non-epithelial members.

Determination of 50% of the sequence of the astrocyte-specific intermediate filament (IF) protein documents the hypervariable regions as well as parts of the coiled-coil array of glial fibrillary acidic protein (GFA). The results show that the four non-epithelial IF proteins (myogenic desmin, mesenchymal vimentin, GFA and neurofilament 68 K protein) known to form homopolymers are much more closely related than the epithelial keratins, which seem to form heteropolymers only. Of the four non-epithelial proteins, desmin and vimentin are the most closely related, since GFA has a shorter non-alpha-helical array at the amino terminus. We discuss the possibility that the non-alpha-helical terminal arrays, because of their sequence and length variability, are responsible for differences of distinct IF with respect to physical-chemical properties such as the low ionic strength-induced depolymerization into protofilaments.

Amino Acid Sequence↗
PubMed1985

Antibodies to intermediate filament proteins. The differential diagnosis of cutaneous tumors.

One hundred cutaneous tumors were investigated immunohistopathologically for the expression of intermediate filament (IF) proteins. Epithelial tumors, such as basocellular and squamous cell carcinomas, cutaneous adnexal tumors, and metastatic carcinomas showed keratin positivity in a varying number of tumor cells with two keratin antibodies with different specificities. Neoplastic cells of fibrohistiocytic tumors, pigmented nevi, melanomas, hemangiomas, glomus tumors, and lymphomas were positive for vimentin, but not for keratin or desmin. Cutaneous leiomyomas and leiomyosarcomas, on the other hand, were positive for desmin. The results show that the typing of IFs enables the differential diagnosis between carcinomas and sarcomas or melanomas, epidermal appendage tumors, and mesenchymal tumors, and between fibrohistiocytic and leiomyocytic tumors, and therefore are of diagnostic value in histopathologic problems of the skin.

Adenocarcinoma↗
PubMed2003

Loss of keratin 6 (K6) proteins reveals a function for intermediate filaments during wound repair.

The ability to heal wounds is vital to all organisms. In mammalian tissues, alterations in intermediate filament (IF) gene expression represent an early reaction of cells surviving injury. We investigated the role of keratin IFs during the epithelialization of skin wounds using a keratin 6alpha and 6beta (K6alpha/K6beta)-null mouse model. In skin explant culture, null keratinocytes exhibit an enhanced epithelialization potential due to increased migration. The extent of the phenotype is strain dependent, and is accompanied by alterations in keratin IF and F-actin organization. However, in wounded skin in vivo, null keratinocytes rupture as they attempt to migrate under the blood clot. Fragility of the K6alpha/K6beta-null epidermis is confirmed when applying trauma to chemically treated skin. We propose that the alterations in IF gene expression after tissue injury foster a compromise between the need to display the cellular pliability necessary for timely migration and the requirement for resilience sufficient to withstand the rigors of a wound site.

Animals↗
PubMed1986

[Immunohistochemical research on human breast tumors using monoclonal antibodies to intermediate filament proteins. Cancer of the breast].

Immunomorphologic study of 29 breast cancer cases using monoclonal antibodies to proteins of intermediate filaments shown to differentiate the lining epithelium from myoepithelium in the non-proliferating epithelial structures of the mamma, has shown the cells in the majority of tumours (according to the International WHO Classification defined as infiltrating ductal, lobular, and tubular cancer forms) to contain prekeratin (PK) C12, specific for normal lining epithelium, but not for the myoepithelium. In cases of cancer with chondroid metaplasia (a malignant variant of the so-called "mixed tumour") the cells contained PK E3, vimentin and structural myosin, normally specific for myoepithelium. The cell heterogenicity in PK C12 content or its absence noted in the infiltrating cancers with predominance of a solid component can indicate a high degree of tumour anaplasia. It is concluded that usage of monoclonal antibodies to PK C12, invariably found in the cells of fibrotic invasion foci, can be a useful indicator for early diagnosis of infiltrative tumour growth.

Antibodies, Monoclonal↗
PubMed2004

Temporal patterns of the embryonic intermediate filaments nestin and vimentin expression in the cerebral cortex of adult rats after cryoinjury.

The expression of two embryonic intermediate filaments, nestin and vimentin, in the rat brain at days 0 (control), 1, 4, 7 and 14 post-cryoinjury was studied to elucidate their roles in brain injury. Western blot analysis showed that both nestin and vimentin expressions in the ipsilateral cerebral cortex were significantly increased at 4 and 7 days post-cryoinjury, and were decreased at day 14 after cryoinjury. Immunohistochemistry showed that there were few nestin- and vimentin-positive cells in the cerebral cortex in normal controls. On days 4 and 7 post-injury, abundant glial cells in the periphery of the lesion were immunostained for nestin and/or vimentin; only vimentin was detected in the majority of inflammatory cells in the core lesion. These findings suggest that nestin and vimentin contribute to the repair of brain injury through the migration of activated cells and the formation of a glial scar.

Animals↗
PubMed1985

Organization of a type I keratin gene. Evidence for evolution of intermediate filaments from a common ancestral gene.

The genomic structure of the mouse 59-kDa keratin gene, a Type I intermediate filament (IF) gene is presented. A comparison of the organization of this gene with that of the human 67-kDa keratin, a Type II IF gene, and hamster vimentin, a Type III IF gene, suggests a common evolutionary origin for Type I, II, and III IF genes. Most introns in these three types of IF genes occur at similar positions within the region encoding sequences predicted to form coiled-coils, but do not delineate structural subdomains. Interestingly though, most of the introns interrupt at or near the beginning of the characteristic 7-residue (heptad) repeat of sequences which form the coiled-coil. These data suggest that the three types of IF genes arose from a common ancestor which may have been assembled from smaller units containing multiple heptad repeats. Subsequent duplication events may then have formed the three known alpha-helical types and each of their various members.

Animals↗
PubMed1985

Structure of the mouse glial fibrillary acidic protein gene: implications for the evolution of the intermediate filament multigene family.

We report the complete sequence of the gene encoding mouse glial fibrillary acidic protein (GFAP), the intermediate filament (IF) protein specific to astrocytes. The 9.8 kb gene includes nine exons separated by introns ranging in size from 0.2 to 2.5 kb. A comparison of the organization of the GFAP gene with that of genes encoding other IF proteins reveals that the structure of IF genes is highly conserved in spite of considerable divergence at the amino acid level. Thus, most of the evolutionary events leading to the placement of introns in IF genes must have occurred prior to the duplication and subsequent divergence of IF genes from a presumptive common ancestral sequence. The conserved gene organization is unrelated to structural features of IF proteins. A curious feature of the GFAP gene is the large number of repeated sequences found in the introns. Six tracts of reiterated di- or trinucleotides are present, plus tandem repeats of two different novel sequences. One repeat is unique to the GFAP gene; the other occurs elsewhere in the mouse genome, although at relatively low frequency.

Animals↗
PubMedDate not supplied

Epstein-Barr virus DNA, intermediate filaments and epithelial membrane antigen in nasopharyngeal carcinoma.

The aim of this study was to investigate the expression of intermediate filaments (cytokeratin, vimentin), epithelial membrane antigen (EMA) and the presence of Epstein-Barr virus (EBV) DNA in undifferentiated nasopharyngeal carcinoma (NPC). A high incidence of nuclear signals in NPC was found in primaries and regional lymph node metastases (70%), using 35S-labelled probes of EBV plasmids for in-situ hybridization. Keratinizing squamous cell carcinomas were EBV-negative. All carcinomas were immuno-reactive for cytokeratin (KL-1). 45% of the carcinomas were positive for vimentin. The expression of epithelial membrane antigen was restricted to epithelial cells and reduced in NPC as compared to the distribution pattern of cytokeratin. Both EBV DNA and vimentin in NPC were present in 9 cases. However, in 5 cases NPC were harboring EBV but were not immunoreactive for anti-vimentin antibodies. In no case was a vimentin-positive NPC also EBV-negative. The identification of cytokeratin subtypes revealed no specific cytokeratin pattern in NPC. The expression of vimentin in NPC is not specific for EBV, but seems to reflect the loss of inter-epithelial contact in anaplastic carcinomas.

Adult↗
PubMed2000

Formation of intermediate filament protein aggregates with disparate effects in two transgenic mouse models lacking the neurofilament light subunit.

Protein aggregates containing intermediate filaments (IFs) are a hallmark of degenerating spinal motor neurons in amyotrophic lateral sclerosis (ALS). Recently, we reported that a deficiency in neurofilament light subunit (NF-L), a phenomenon associated with ALS, promoted the formation of IF inclusions with ensuing motor neuron death in transgenic mice overproducing peripherin, a type III IF protein detected in axonal inclusions of ALS patients. To further assess the role of NF-L in the formation of abnormal IF inclusions, we generated transgenic mice overexpressing human neurofilament heavy subunits (hNF-H) in a context of targeted disruption of the NF-L gene (hH;L-/- mice). The hH;L-/- mice exhibited motor dysfunction, and they developed nonfilamentous protein aggregates containing NF-H and peripherin proteins in the perikarya of spinal motor neurons. However, the perikaryal protein aggregates in the hH;L-/- mice did not provoke motor neuron death, unlike toxic IF inclusions induced by peripherin overexpression in NF-L null mice (Per;L-/- mice). Our results indicate that different types of IF protein aggregates with distinct properties may occur in a context of NF-L deficiency and that an axonal localization of such aggregates may be an important factor of toxicity.

Animals↗
PubMed1989

Multiple mRNAs encode peripherin, a neuronal intermediate filament protein.

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. Antibodies eluted from the fusion proteins produced by clones 3u and 5g recognize the peripherin spots on immunoblots. Where they overlap the three cDNAs have identical sequences. cDNA 5g exhibits the closest homology to type III IFP cDNAs. cDNA 3u is identical to the corresponding region of cDNA 5g, except for the insertion of a 96 bp fragment at a position corresponding to the junction of exons 4 and 5 in type III IFP cDNAs. cDNA 5b is also identical to the corresponding region of cDNA 5g, except for the deletion of a 62 bp fragment at the junction of exons 8 and 9 in type III IFP cDNAs. S1 mapping experiments performed with probes covering the 3' end of the two unexpected regions show that three distinct mRNAs correspond to the three cDNAs. Moreover, three peripherin products, two minor 61 and 56 kd products in addition to the major 58 kd peripherin, are observed when poly(A)+ RNA is in vitro translated, the 61 kd peripherin being translated from the 3u-selected RNA. The three RNAs originate from alternative splicing of a unique peripherin gene, thus generating polymorphism of peripherin.

Amino Acid Sequence↗
PubMed1986

Effects of colcemid and taxol on microtubules and intermediate filaments in chick embryo fibroblasts.

Reports on how changes in microtubule (MT) distribution or polymerization affect the distribution of intermediate filaments (IFs) differ. Therefore, we have used cytoimmunofluorescence techniques and electron microscopy to systematically examine and compare the arrangements of MTs and IFs in cultures of chick embryo fibroblasts under the following conditions: at different times during the cell cycle, in the presence of Colcemid or of taxol, in the presence of both drugs in succession or simultaneously in varying ratios, and during recovery from treatment with Colcemid or taxol. We have found that depolymerization of MTs by 1 microM Colcemid resulted in the rapid formation of massive IF-cables, structures distinct from "collapsed IFs" or "juxtanuclear coils." Neither the rapid formation of IF-cables nor their dispersion during recovery required protein synthesis. Cells treated with 10 microM taxol rapidly formed MT-bundles, as well as aggregates of intertwining IFs, termed "IF-skeins." MT-bundles and IF-skeins displayed strikingly complementary distributions. This reciprocal distribution of packed MTs and IFs was also obvious in untreated anaphase and telophase cells. When 10 microM taxol and 1 microM Colcemid were applied simultaneously, the complementary distributions of MT-bundles and IF-skeins mimicked those in taxol alone. This ability of taxol to block Colcemid's effects was concentration dependent. Decreasing the taxol: Colcemid ratio allowed the depolymerization of MTs, which correlated with the formation of IF-cables.

Alkaloids↗
PubMed1995

Changes in the expression of intermediate filaments and desmoplakins during development of human notochord.

Indirect immunofluorescence was used to study the expression of desmosomal and intermediate filament (IF) proteins in the human notochord between the 4th and 12th weeks of embryonic development. Towards the end of this period, the development of the notochord is characterized by its gradual physiological atrophy and disappearance inside the vertebral bodies. In all of our embryos, the notochord cells expressed cytokeratin and vimentin but not desmin, neurofilament protein or glial fibrillary acidic protein. Throughout the stages studied, the expression of cytokeratin was strong. Vimentin expression, on the other hand, changed during the stages studied. In our youngest embryos, vimentin could be detected only in the peripheral cells of the notochord. During development, a distinct increase occurred in vimentin expression, and in the oldest embryos, all notochord cells showed bright vimentin-specific fluorescence. Simultaneously with this modification, a change occurred in the expression of desmosomal proteins: The notochord cells expressed desmoplakins abundantly during early stages, but weakly or not at all during later stages. Correspondingly, electron microscopy of the same stages showed a striking decrease in the number of desmosomes between notochord cells. Our results confirm that, during early development, the notochord displays features specific for epithelial cells. This accords with the view that notochord is of epithelial origin. The modifications observed in the expression of IF and desmosomal proteins were temporally correlated with developmentally regulated atrophy of the notochord. The programmed regression of the notochord cells is thus associated with a switch from a predominantly epithelial phenotype to a more mesenchymal one.

Cytoskeletal Proteins↗
PubMed2007

Oxidation and nitrosylation of cysteines proximal to the intermediate filament (IF)-binding site of plectin: effects on structure and vimentin binding and involvement in IF collapse.

As an intermediate filament (IF)-based cytolinker protein, plectin plays a key role in the maintenance of cellular cytoarchitecture and serves at the same time as a scaffolding platform for signaling cascades. Consisting of six structural repeats (R1-6) and harboring binding sites for different IF proteins and proteins involved in signaling, the plectin C-terminal domain is of strategic functional importance. Depending on the species, it contains at least 13 cysteines, 4 of which reside in the R5 domain. To investigate the structural and biological functions of R5 cysteines, we used cysteine-to-serine mutagenesis and spectroscopic, biochemical, and functional analyses. Urea-induced unfolding experiments indicated that wild-type R5 in the oxidized, disulfide bond-mediated conformation was more stable than its cysteine-free mutant derivative. The binding affinity of R5 for vimentin was significantly higher, however, when the protein was in the reduced, more relaxed conformation. Of the four R5 cysteines, one (Cys4) was particularly reactive as reflected by its ability to form disulfide bridges with R5 Cys1 and to serve as a target for nitrosylation in vitro. Using immortalized endothelial cell cultures from mice, we show that endogenous plectin is nitrosylated in vivo, and we found that NO donor-induced IF collapse proceeds dramatically faster in plectin-deficient compared with wild-type cells. Our data suggest an antagonistic role of plectin in nitrosylation (oxidative stress)-mediated alterations of IF cytoarchitecture and a possible role of R5 Cys4 as a regulatory switch.

Amino Acid Sequence↗