Alterations In Intermediate Filaments Research Articles

Intermediate filaments: primary determinants of cell architecture and plasticity

Intermediate filaments (IFs) are major constituents of the cytoskeleton and nuclear boundary in animal cells. They are of prime importance for the functional organization of structural elements. Depending on the cell type, morphologically similar but biochemically distinct proteins form highly viscoelastic filament networks with multiple nanomechanical functions. Besides their primary role in cell plasticity and their established function as cellular stress absorbers, recently discovered gene defects have elucidated that structural alterations of IFs can affect their involvement both in signaling and in controlling gene regulatory networks. Here, we highlight the basic structural and functional properties of IFs and derive a concept of how mutations may affect cellular architecture and thereby tissue construction and physiology.

Alterations of hepatocellular intermediate filaments during extrahepatic cholestasis in rat liver.

Intermediate filaments (IF) maintain the structural and functional integrity of cells. To investigate whether IF change as a consequence of increased mechanical pressure and what the significance of such alterations is for the integrity of hepatocytes, we investigated alterations of IF in rat liver following common bile duct ligation (CBDL). Immunofluorescence of cytokeratin 18 was performed on extracted cryostat sections which were also used for electron microscopy. Ultrathin sections of mildly extracted liver tissue were applied to reveal the relationship between IF and intercellular junctions and cytoplasmic organelles. Our results showed that hepatocellular IF underwent striking changes during CBDL. The so-called pericanalicular sheath disappeared and IF were rigidly rearranged at the cell periphery, appearing as honeycomb-like structures. Increased amounts of IF were found in close association with increased numbers of desmosomes at the lateral membranes of hepatocytes, and electron-dense desmosome-like bodies were even observed in the ectoplasm at bile canaliculi. Rearrangement of IF in the cytoplasm resulted in segregation of subcellular compartments. The increased density of the IF network and desmosomes are compensatory mechanisms of hepatocytes to resist increased mechanical load and disperse the tension. However, the intracellular rearrangement of IF leading to segregation of subcellular compartments may also have distinct effects on hepatocellular metabolic functions.

Altered intermediate filament expression in human neuroblastoma cells transformed by a growth-promoting agent derived from schizophrenic CSF.

1. Transformed (TR) cell lines showed faster doubling times and higher cell densities at confluence, as well as altered morphology, changing from flat epitheloid to smaller round or bipolar shapes. Since such morphological changes are suggestive of alterations in intermediate filaments, we have analyzed the expression of both vimentin and neurofilament. 2. Immunohistochemical analysis of vimentin showed a redistribution from a cytoplasmic network to a perinuclear accumulation in TR cell lines. 3. Western blot analysis demonstrated that the vimentin content was decreased 60-90%. The content of the 70-kD neurofilament protein was also decreased in TR cells, but its intracellular distribution was indistinguishable from that in the control cell lines.

The mammalian stress response and the cytoskeleton: alterations in intermediate filaments.

Annals of the New York Academy of SciencesVolume 455, Issue 1 p. 57-67 The Mammalian Stress Response and the Cytoskeleton: Alterations in Intermediate Filamentsa W. J. WELCH, W. J. WELCH Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724Search for more papers by this authorJ. R. FERAMISCO, J. R. FERAMISCO Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724Search for more papers by this authorS. H. BLOSE, S. H. BLOSE Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724Search for more papers by this author W. J. WELCH, W. J. WELCH Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724Search for more papers by this authorJ. R. FERAMISCO, J. R. FERAMISCO Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724Search for more papers by this authorS. H. BLOSE, S. H. BLOSE Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724Search for more papers by this author First published: October 1985 https://doi.org/10.1111/j.1749-6632.1985.tb50403.xCitations: 41 a W. J. W. is supported by a National Institutes of Health grant (GM 33551), S. H. B. by a National Heart, Lung, and Blood Institute grant (HL 23848), and J. R. F. by a National Institutes of Health grant (GM 28277). AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume455, Issue1Intermediate FilamentsOctober 1985Pages 57-67 RelatedInformation