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Urban Lendahl - One of the best experts on this subject based on the ideXlab platform.
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Pediatric Rhabdomyosarcomas Express the Intermediate Filament Nestin
Pediatric Research, 1998Co-Authors: Miyuki Kobayashi, Urban Lendahl, Gunnar Sjöberg, Stefan Söderhäll, Bengt Sandstedt, Thomas SejersenAbstract:Previous findings that the Intermediate Filament nestin is expressed in immature skeletal muscle cells prompted us to compare the staining patterns of nestin and desmin in rhabdomyosarcomas (RMSs) and in other small cell tumors of infancy. We found that nestin immunoreactivity was present in all of 29 examined typical RMSs, which also expressed desmin. Two undifferentiated tumors, primarily suspected to be RMSs, expressed nestin, but not desmin. One of these nestin-positive, desmin-negative tumors was positive for the expression of the myogenic regulatory gene MyoD and is considered to represent an undifferentiated RMS. The other, a paratesticular tumor, did not contain transcripts for MyoD, and most likely does not represent a RMS. In several RMSs and nonmuscle tumors, a z-disc-associated nestin immunoreactivity occurred as a paramalignant phenomenon in cross-striated muscle fibers adjacent to the tumor cells. Our findings indicate that nestin, although present also in tumors of the central and peripheral nervous systems, as well as in endothelial cells and in some muscle cells adjacent to tumors, is a useful complementary marker for RMS, particularly in very undifferentiated desmin-negative tumors.
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Expression of the neuroectodermal Intermediate Filament nestin in human melanomas.
Cancer Research, 1994Co-Authors: Vivi Ann Florenes, Ola Myklebost, Ruth Holm, Urban Lendahl, Øystein FodstadAbstract:Nestin is a newly identified Intermediate Filament expressed in proliferating neuronal progenitor cells, but not in the adult brain. Nestin expression reappears in many tumors of the central nervous system and has in human glioblastomas been associated with a high degree of malignancy. Because melanocytes are of neuroectodermal origin, we studied nestin expression in benign and malignant cells of the melanocytic lineage using Northern blot and immunohistochemical analyses. Nestin mRNA was detected in 24 of 34 metastatic melanomas and in 1 of 4 benign nevi, whereas the protein was expressed in 10 of 15 primary melanomas, in 29 of 34 metastatic tumors, and in 3 of 4 nevi. Neither normal melanocytes nor any of 4 basal cell carcinomas showed detectable levels of the protein. The high fraction of melanocytic tumors which express nestin, particularly the metastatic melanomas, suggests that nestin may be a useful marker for such malignancies. Furthermore, although no significant correlation between nestin expression and tumor malignancy was observed, the protein was most abundantly expressed in the infiltrating part of the tumors, indicating a possible involvement of nestin in tumor invasion.
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transient expression of the Intermediate Filament nestin during skeletal muscle development
Journal of Cell Science, 1993Co-Authors: Thomas Sejersen, Urban LendahlAbstract:It has previously been established that skeletal muscle development is accompanied by changes in the composition of Intermediate Filaments: vimentin is expressed predominantly in myoblasts and desmin in adult myotubes. We show that the Intermediate Filament transitions during muscle development are more complex, and involve a transient expression of the recently discovered Intermediate Filament nestin. Nestin RNA is expressed predominantly early, in a biphasic pattern, and is markedly downregulated in adult rat muscle, whereas desmin RNA becomes more abundant throughout development. Nestin protein was found up to the postnatal myotube stage, where it colocalized with desmin in Z bands. The intracellular distribution of nestin, vimentin and desmin was analysed in the human myogenic cell line G6 before and after in vitro differentiation. Despite its more distant evolutionary and structural relationship to the other two Intermediate Filaments, nestin formed a cytoplasmic Filamentous network indistinguishable from that of desmin and vimentin, both in undifferentiated myoblasts and after differentiation to multinuclear myotubes. In conclusion, our data suggest that nestin is an integrated component of the dynamic Intermediate Filament network during muscle development and that nestin copolymerizes with desmin and vimentin at stages of coexpression.
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cns stem cells express a new class of Intermediate Filament protein
Cell, 1990Co-Authors: Urban Lendahl, Lyle B Zimmerman, Ronald D G MckayAbstract:Multipotential CNS stem cells receive and implement instructions governing differentiation to diverse neuronal and glial fates. Exploration of the mechanisms generating the many cell types of the brain depends crucially on markers identifying the stem cell state. We describe a gene whose expression distinguishes the stem cells from the more differentiated cells in the neural tube. This gene was named nestin because it is specifically expressed in neuroepithelial stem cells. The predicted amino acid sequence of the nestin gene product shows that nestin defines a distinct sixth class of Intermediate Filament protein. These observations extend a model in which transitions in Intermediate Filament gene expression reflect major steps in the pathway of neural differentiation.
Bishr M Omary - One of the best experts on this subject based on the ideXlab platform.
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Intermediate Filament proteins of digestive organs physiology and pathophysiology
American Journal of Physiology-gastrointestinal and Liver Physiology, 2017Co-Authors: Bishr M OmaryAbstract:Intermediate Filament proteins (IFs), such as cytoplasmic keratins in epithelial cells and vimentin in mesenchymal cells and the nuclear lamins, make up one of the three major cytoskeletal protein ...
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assays for posttranslational modifications of Intermediate Filament proteins
Methods in Enzymology, 2016Co-Authors: Natasha T Snider, Bishr M OmaryAbstract:Intermediate Filament (IF) proteins are known to be regulated by a number of posttranslational modifications (PTMs). Phosphorylation is the best-studied IF PTM, whereas ubiquitination, sumoylation, acetylation, glycosylation, ADP-ribosylation, farnesylation, and transamidation are less understood in functional terms but are known to regulate specific IFs under various contexts. The number and diversity of IF PTMs is certain to grow along with rapid advances in proteomic technologies. Therefore, the need for a greater understanding of the implications of PTMs to the structure, organization, and function of the IF cytoskeleton has become more apparent with the increased availability of data from global profiling studies of normal and diseased specimens. This chapter will provide information on established methods for the isolation and monitoring of IF PTMs along with the key reagents that are necessary to carry out these experiments.
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Intermediate Filament proteins and their associated diseases
The New England Journal of Medicine, 2004Co-Authors: Bishr M Omary, Pierre A Coulombe, W Irwin H McleanAbstract:Intermediate Filaments provide scaffolding for the cell and protect it against stress. This comprehensive review points out that there are more than 100 Intermediate Filament genes and that mutant Intermediate Filament proteins cause more than 30 diseases. Selective expression of these genes in particular tissues accounts for tissue-specific diseases caused by mutant Intermediate Filament genes, such as epidermolysis bullosa simplex and certain types of cardiomyopathy.
David A Weitz - One of the best experts on this subject based on the ideXlab platform.
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mechanical properties of vimentin Intermediate Filament networks
Biophysical Journal, 2014Co-Authors: Mikkel H Jensen, Ming Guo, David A WeitzAbstract:One marker of mesenchymal cells is the expression of vimentin Intermediate Filament (VIF) proteins, which assemble into networks. The cytoskeleton is typically comprised of these Intermediate Filament networks, actin, and microtubules. While some aspects of VIF networks have been characterized in bulk, their mechanical properties in situ have not been well defined. Here we use microrheological techniques to study VIF network mechanics in cells in which microtubules and actin have been removed so that VIF can be studied independently of the other cytoskeletal components. Simultaneous imaging of the network allows us to correlate network structure with its local mechanical properties.
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divalent cations crosslink vimentin Intermediate Filament tail domains to regulate network mechanics
Journal of Molecular Biology, 2010Co-Authors: Yichia Lin, Harald Herrmann, Chase P Broedersz, Amy C Rowat, Tatjana Wedig, F C Mackintosh, David A WeitzAbstract:Abstract Intermediate Filament networks in the cytoplasm and nucleus are critical for the mechanical integrity of metazoan cells. However, the mechanism of crosslinking in these networks and the origins of their mechanical properties are not understood. Here, we study the elastic behavior of in vitro networks of the Intermediate Filament protein vimentin. Rheological experiments reveal that vimentin networks stiffen with increasing concentrations of Ca2+ and Mg2+, showing that divalent cations act as crosslinkers. We quantitatively describe the elastic response of vimentin networks over five decades of applied stress using a theory that treats the divalent cations as crosslinkers: at low stress, the behavior is entropic in origin, and increasing stress pulls out thermal fluctuations from single Filaments, giving rise to a nonlinear response; at high stress, enthalpic stretching of individual Filaments significantly modifies the nonlinearity. We investigate the elastic properties of networks formed by a series of protein variants with stepwise tail truncations and find that the last 11 amino acids of the C-terminal tail domain mediate crosslinking by divalent ions. We determined the single-Filament persistence length, lP ≈ 0.5 μm, and Young's modulus, Y ≈ 9 MPa; both are consistent with literature values. Our results provide insight into a crosslinking mechanism for vimentin networks and suggest that divalent ions may help regulate the cytoskeletal structure and mechanical properties of cells.
Andrew L Folpe - One of the best experts on this subject based on the ideXlab platform.
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Aberrant Intermediate Filament and synaptophysin expression is a frequent event in malignant melanoma: an immunohistochemical study of 73 cases
Modern Pathology, 2015Co-Authors: Ryan C Romano, Jodi M Carter, Andrew L FolpeAbstract:Malignant melanomas are known to express vimentin, among other Intermediate Filaments. Though anomalous keratin expression by malignant melanoma has been reported, its frequency is not well-established and this phenomenon is not well-known. We have seen in consultation a number of malignant melanomas with anomalous expression of keratin, other Intermediate Filaments, or synaptophysin, and therefore studied a large group of primary and metastatic melanomas to determine the frequency of these events. About 73 cases of malignant melanoma (22 primaries and 51 metastases) from 71 patients (51 male, 20 female; mean 59 years, range 17–87 years) were retrieved from our archives. Prior diagnoses were confirmed by re-review of hematoxylin and eosin sections and relevant (e.g., S100 protein, HMB45, Melan-A, and tyrosinase) immunohistochemical studies. Available sections were immunostained for keratin (OSCAR and AE1/AE3 antibodies), desmin, neuroFilament protein, glial fibrillary acidic protein, synaptophysin, and chromogranin A. Not all cases could be tested for all markers. Cases were predominantly epithelioid (48/73, 66%) or spindle cell/desmoplastic (25/73, 34%). S100 protein, Melan-A, HMB45, and tyrosinase were positive in 60/65 (92%), 34/64 (53%), 30/60 (50%), 25/48 (52%) of cases, respectively. All five S100-protein-negative cases expressed at least one of the other melanocytic markers: Melan-A (two of four, 50%), HMB45 (two of three, 67%), and tyrosinase (one of two, 50%). All cases expressed at least one melanocytic marker. Cases were positive for keratin (OSCAR, 17/61, 28%; AE1/AE3, 16/40, 40%), desmin (11/47, 24%), neuroFilament protein (5/31, 16%), glial fibrillary acidic protein (3/32, 9%), and synaptophysin (10/34, 29%), typically only in a minority of cells. Chromogranin was negative (0/32, 0%). Altogether 9/73 cases (12%) showed expression of >1 Intermediate Filament. All S100-protein-negative melanomas showed anomalous Intermediate Filament expression (keratin—one case, desmin—three cases, neuroFilament protein—one case). Anomalous Intermediate Filament or synaptophysin expression was more common in epithelioid (Intermediate Filament, 27/48, 56%; synaptophysin, 7/22, 32%) as compared with spindle cell/desmoplastic (Intermediate Filament, 8/25, 32%; synaptophysin, 3/12, 25%) melanomas. Overall, 48% (35/73) of cases showed anomalous expression of at least one Intermediate Filament. Anomalous expression of all Intermediate Filaments and synaptophysin was found in significant subsets of malignant melanoma, representing potentially serious diagnostic pitfalls. While the inclusion of consultation cases may inflate the frequency of these findings in this series, similar findings were also seen in institutional cases. Malignant melanoma showing anomalous Intermediate Filament and synaptophysin expression may easily be mistaken for carcinomas, rhabdomyosarcomas, and neuroendocrine tumors. Awareness of this phenomenon, careful histopathological evaluation, and an appropriate melanocytic immunohistochemical panel should facilitate the diagnosis of malignant melanoma with unusual immunophenotypes.
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aberrant Intermediate Filament and synaptophysin expression is a frequent event in malignant melanoma an immunohistochemical study of 73 cases
Modern Pathology, 2015Co-Authors: Ryan C Romano, Jodi M Carter, Andrew L FolpeAbstract:Aberrant Intermediate Filament and synaptophysin expression is a frequent event in malignant melanoma: an immunohistochemical study of 73 cases
Thomas Sejersen - One of the best experts on this subject based on the ideXlab platform.
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Pediatric Rhabdomyosarcomas Express the Intermediate Filament Nestin
Pediatric Research, 1998Co-Authors: Miyuki Kobayashi, Urban Lendahl, Gunnar Sjöberg, Stefan Söderhäll, Bengt Sandstedt, Thomas SejersenAbstract:Previous findings that the Intermediate Filament nestin is expressed in immature skeletal muscle cells prompted us to compare the staining patterns of nestin and desmin in rhabdomyosarcomas (RMSs) and in other small cell tumors of infancy. We found that nestin immunoreactivity was present in all of 29 examined typical RMSs, which also expressed desmin. Two undifferentiated tumors, primarily suspected to be RMSs, expressed nestin, but not desmin. One of these nestin-positive, desmin-negative tumors was positive for the expression of the myogenic regulatory gene MyoD and is considered to represent an undifferentiated RMS. The other, a paratesticular tumor, did not contain transcripts for MyoD, and most likely does not represent a RMS. In several RMSs and nonmuscle tumors, a z-disc-associated nestin immunoreactivity occurred as a paramalignant phenomenon in cross-striated muscle fibers adjacent to the tumor cells. Our findings indicate that nestin, although present also in tumors of the central and peripheral nervous systems, as well as in endothelial cells and in some muscle cells adjacent to tumors, is a useful complementary marker for RMS, particularly in very undifferentiated desmin-negative tumors.
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transient expression of the Intermediate Filament nestin during skeletal muscle development
Journal of Cell Science, 1993Co-Authors: Thomas Sejersen, Urban LendahlAbstract:It has previously been established that skeletal muscle development is accompanied by changes in the composition of Intermediate Filaments: vimentin is expressed predominantly in myoblasts and desmin in adult myotubes. We show that the Intermediate Filament transitions during muscle development are more complex, and involve a transient expression of the recently discovered Intermediate Filament nestin. Nestin RNA is expressed predominantly early, in a biphasic pattern, and is markedly downregulated in adult rat muscle, whereas desmin RNA becomes more abundant throughout development. Nestin protein was found up to the postnatal myotube stage, where it colocalized with desmin in Z bands. The intracellular distribution of nestin, vimentin and desmin was analysed in the human myogenic cell line G6 before and after in vitro differentiation. Despite its more distant evolutionary and structural relationship to the other two Intermediate Filaments, nestin formed a cytoplasmic Filamentous network indistinguishable from that of desmin and vimentin, both in undifferentiated myoblasts and after differentiation to multinuclear myotubes. In conclusion, our data suggest that nestin is an integrated component of the dynamic Intermediate Filament network during muscle development and that nestin copolymerizes with desmin and vimentin at stages of coexpression.