‘Hard’ and ‘soft’ principles defining the structure, function and regulation of keratin intermediate filaments

Coulombe, Pierre A.; Omary, M. Bishr

doi:10.1016/s0955-0674(01)00301-5

Cited by 631 publications

(628 citation statements)

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“…KRT8 is the major type II keratin in the small and large intestine, along with type I keratins KRT18, 19, or 20 dependent on the cell and individual tissue. KRT8 has functional roles in maintenance of normal epithelial architecture (Coulombe and Omary, 2002). Here we observed down-regulation of both KRT8 and KRT18 in mouse colonic mucosa induced by DSS, perhaps as a reflexion of severe damage to the epithelium.…”

Section: Continued) Differentially Expressed Proteins In the Colon Msupporting

confidence: 48%

Preventive Effects of Spirogyra neglecta and a Polysaccharide Extract against Dextran Sodium Sulfate Induced Colitis in Mice

Taya

Kakehashi²,

Wongpoomchai³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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Ulcerative colitis (UC) results from colonic epithelial barrier defects and impaired mucosal immune responses. In this study, we aimed to investigate the modifying effects of a Spirogyra neglecta extract (SNE), a polysaccharide extract (PE) and a chloroform fraction (CF) on dextran sodium sulfate (DSS)-induced colitis in mice and to determine the mechanisms. To induce colitis, ICR mice received 3% DSS in their drinking water for 7 days. Seven days preceding the DSS treatment, oral administration of SNE, PE and CF at doses of 50, 25 and 0.25 mg/kg body weight (low dose), 200, 100 and 1 mg/kg body weight (high dose) and vehicle was started and continued for 14 days. Histologic findings showed that DSS-induced damage of colonic epithelial structure and inflammation was attenuated in mice pre-treated with SNE, PE and CF. Furthermore, SNE and PE significantly protected colonic epithelial cells from DSS-induced cell cycle arrest, while SNE, PE and CF significantly diminished apoptosis. Proteome analysis demonstrated that SNE and PE might ameliorate DSS-induced colitis by inducing antioxidant enzymes, restoring impaired mitochondria function, and regulating inflammatory cytokines, proliferation and apoptosis. These results suggest that SNE and PE could prevent DSS-induced colitis in ICR mice by protection against and/or aiding recovery from damage to the colonic epithelium, reducing ROS and maintaining normal mitochondrial function and apoptosis.

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Section: Continued) Differentially Expressed Proteins In the Colon Msupporting

confidence: 48%

Preventive Effects of Spirogyra neglecta and a Polysaccharide Extract against Dextran Sodium Sulfate Induced Colitis in Mice

Taya

Kakehashi²,

Wongpoomchai³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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“…In most cells, K19 was expressed at higher levels and, rather than incorporating into filaments, it instead accumulated in punctate structures in the cytoplasm that labeled with antibodies specific for hK19 ( Figure 1B). Expressed together, myc-K8 and hK19 coassembled into thickly bundled, filamentlike arrays (Figure 1, D-F), as expected (Fuchs and Weber, 1994;Coulombe and Omary, 2002).…”

Section: Dys-abd Associates Specifically With Filaments Containing K8mentioning

confidence: 52%

“…COS-7 cells contain vimentin and endogenous cytokeratins (Niessen et al, 1997) that, although not fully characterized, include K8 and K18 (our unpublished data). Overexpression of myc-K8 in COS-7 cells resulted in its incorporation into filamentous structures that labeled with antibodies to the myc epitope tag ( Figure 1A), perhaps due to the ability of K8 to associate with endogenous K18 (Fuchs and Weber, 1994;Coulombe and Omary, 2002). The overexpression of hK19 in COS-7 cells produced two types of structures.…”

Section: Dys-abd Associates Specifically With Filaments Containing K8mentioning

confidence: 99%

“…We showed further that K8 and K19 copurify with the dystrophin-glycoprotein complex. K8, a type II cytokeratin, and K19, a type I cytokeratin, coassemble to form intermediate filaments in other cells (Fuchs and Weber, 1994;Coulombe and Omary, 2002) and are likely to do so in muscle as well. Indeed, in addition to their presence at costameres, K8 and K19 also associated with the Z-disks of sarcomeres deep in the myoplasm (Ursitti et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…We also examined the ability of the Dys-ABD to associate with filaments composed of K8 and K18. These two cytokeratin subunits together form filaments (Fuchs and Weber, 1994;Coulombe and Omary, 2002), but K18 is not expressed at significant levels in mature striated muscle (Kosmehl et al, 1990;Ursitti et al, 2004). When coexpressed in COS-7 cells, K8 and K18 assembled into filamentous arrays ( Figure 2E), but these did not associate with the Dys-ABD (Figure 2, D and F).…”

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confidence: 98%

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Specific Interaction of the Actin-binding Domain of Dystrophin with Intermediate Filaments Containing Keratin 19

Stone

O’Neill

Catino

et al. 2005

MBoC

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Cytokeratins 8 and 19 concentrate at costameres of striated muscle and copurify with the dystrophin-glycoprotein complex, perhaps through the interaction of the cytokeratins with the actin-binding domain of dystrophin. We overexpressed dystrophin's actin-binding domain (Dys-ABD), K8 and K19, as well as closely related proteins, in COS-7 cells to assess the basis and specificity of their interaction. Dys-ABD alone associated with actin microfilaments. Expressed with K8 and K19, which form filaments, Dys-ABD associated preferentially with the cytokeratins. This interaction was specific, as the homologous ABD of ␤I-spectrin failed to interact with K8/K19 filaments, and Dys-ABD did not associate with desmin or K8/K18 filaments. Studies in COS-7 cells and in vitro showed that Dys-ABD binds directly and specifically to K19. Expressed in muscle fibers in vivo, K19 accumulated in the myoplasm in structures that contained dystrophin and spectrin and disrupted the organization of the sarcolemma. K8 incorporated into sarcomeres, with no effect on the sarcolemma. Our results show that dystrophin interacts through its ABD with K19 specifically and are consistent with the idea that cytokeratins associate with dystrophin at the sarcolemma of striated muscle. INTRODUCTIONMutations in the gene for dystrophin cause Duchenne or Becker Muscular Dystrophy, but we still know little about dystrophin's functions in normal muscle or how its absence leads to the loss of myofibers. Dystrophin is the major cytoskeletal component of a large, transmembrane complex (Ahn and Kunkel, 1993;Matsumura and Campbell, 1994;Ozawa et al., 1998) that plays a role in signaling from the plasma membrane of skeletal myofibers (sarcolemma) to the cytoplasm (Rando, 2001;Lapidos et al., 2004) and in transmitting the force of contraction across the sarcolemma to extracellular structures (Campbell, 1995;Bloch and Gonzalez-Serratos, 2003). Here, we focus on the latter role, and particularly, on the nature of the connections made between the contractile apparatus and the sarcolemma, at sites termed "costameres" (Bloch and Gonzalez-Serratos, 2003;Ervasti, 2003).Costameres are riblike structures that surround each myofiber at the sarcolemma and that are enriched in a number of integral and peripheral membrane proteins (Bloch and Gonzalez-Serratos, 2003;Ervasti, 2003), including dystrophin (Masuda et al., 1992;Minetti et al., 1992;Porter et al., 1992;Straub et al., 1992;Williams and Bloch, 1999a;Rybakova et al., 2000). Costameres and the connections between the contractile apparatus and the sarcolemma that they anchor are present at the plasma membrane overlying both the Z and M lines of superficial myofibrils of fast-twitch muscles (Porter et al., 1992;Williams et al., 2000). They also can be oriented at the plasma membrane parallel to the longitudinal axis of the myofibers, creating a rectilinear, structural lattice at the sarcolemma. Dystrophin and its associated proteins are enriched at all these sites (Porter et al., 1992;Williams and Bloch, 1999a;Williams et al...

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Molecular Genetics of Inherited Disorders of Epidermal Keratins

Sprecher

2009

Encyclopedia of Life Sciences

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Keratins are a major constituent of the epidermal cell cytoskeleton. Apart from their contribution to cell ability to resist mechanical stress, they have been shown to regulate additional biological processes of importance such as protein synthesis, cell migration and apoptosis. Much of this knowledge has been gained through the study of rare disorders, known as keratinopathies, which are caused by mutations in genes encoding the various epidermal keratins . Recently, novel therapeutic approaches for keratin disorders have been tested successfully, thus raising new hopes for the treatment of this group of inherited skin diseases. Key concepts Keratins are major constituent of epithelial cell cytoskeleton and confer to the cell the ability to resist mechanical stress. Keratins play additional nonstructural role such regulation of cell growth, protein synthesis, cell migration and apoptosis. Keratin disorders manifest with clinical and pathological features that reflect the site of expression of the mutant keratins and the specific function of the keratin domain affected by the causative mutation. Keratin disorders are characterized by genetic heterogeneity, namely a single clinical phenotype can result from mutations in different (but sometimes functionally related) genes (e.g. epidermolysis bullosa caused by mutations in at least five genes). Keratin disorders are characterized by phenotypic heterogeneity, namely mutations in the very same gene can give rise to multiple distinct phenotypes (e.g. mutations in KRT1 can cause at least four distinct diseases). Keratin mutations exert a dominant negative effect; hence current approaches are aimed at eliminating the mutant proteins from the skin. Based on this concept, a first clinical trial in humans has recently been launched to test the effect of a siRNA to treat pachyonychia congenita.

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‘Hard’ and ‘soft’ principles defining the structure, function and regulation of keratin intermediate filaments

Cited by 631 publications

References 94 publications

Preventive Effects of Spirogyra neglecta and a Polysaccharide Extract against Dextran Sodium Sulfate Induced Colitis in Mice

Preventive Effects of Spirogyra neglecta and a Polysaccharide Extract against Dextran Sodium Sulfate Induced Colitis in Mice

Specific Interaction of the Actin-binding Domain of Dystrophin with Intermediate Filaments Containing Keratin 19

Molecular Genetics of Inherited Disorders of Epidermal Keratins

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