Structural and regulatory functions of keratins

Magin, Thomas M.; Vijayaraj, Preethi; Leube, Rudolf E.

doi:10.1016/j.yexcr.2007.03.005

Cited by 270 publications

(219 citation statements)

References 127 publications

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“…They are formed when two already connected cells start to move apart. Type II nanotubes differ from all previously found nanotubes: they have no actin filaments but have cytokeratin filaments, which are probably responsible for their stability [55] and longer life span. They do not seem to be involved in transport between cells, but rather in providing a positional effect to connected cells by sensing their direction of migration and enabling reverted movement along the intercellular tether [9].…”

Section: Membrane Nanotubescontrasting

confidence: 59%

Mechanisms for the formation of membranous nanostructures in cell-to-cell communication

Schara¹,

Janša

Šuštar

et al. 2009

Cellular and Molecular Biology Letters

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Cells interact by exchanging material and information. Two methods of cell-to-cell communication are by means of microvesicles and by means of nanotubes. Both microvesicles and nanotubes derive from the cell membrane and are able to transport the contents of the inner solution. In this review, we describe two physical mechanisms involved in the formation of microvesicles and nanotubes: curvature-mediated lateral redistribution of membrane components with the formation of membrane nanodomains; and plasmamediated attractive forces between membranes. These mechanisms are clinically relevant since they can be affected by drugs. In particular, the underlying mechanism of heparin's role as an anticoagulant and tumor suppressor is the suppression of microvesicluation due to plasma-mediated attractive interaction between membranes.

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Section: Membrane Nanotubescontrasting

confidence: 59%

Mechanisms for the formation of membranous nanostructures in cell-to-cell communication

Schara¹,

Janša

Šuštar

et al. 2009

Cellular and Molecular Biology Letters

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“…The most prominent keratins of basal epidermal cells are the type II K5 and the type I keratins K14 and K15 (14). K5 deletion results in pronounced cytolysis and neonatal lethality (38), whereas K14 depletion leads to epidermolysis bullosa simplex-like disease where mechanical trauma exacerbates blistering (39).…”

Section: Discussionmentioning

confidence: 99%

“…Filament assembly requires both keratin types because of the obligatory heterodimer composition of keratin IFs (13). Given that most epithelia express 4-10 different keratin subunits (14), the total and isotype-specific contribution of the overall keratin network to mechanical properties of epithelia remains highly challenging to analyze in vivo. An additional difficulty in experimentation is the absence of drugs to specifically disrupt the keratin IF system.…”

mentioning

confidence: 99%

Keratins as the main component for the mechanical integrity of keratinocytes

Ramms

Fabris

Windoffer

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Keratins are major components of the epithelial cytoskeleton and are believed to play a vital role for mechanical integrity at the cellular and tissue level. Keratinocytes as the main cell type of the epidermis express a differentiation-specific set of type I and type II keratins forming a stable network and are major contributors of keratinocyte mechanical properties. However, owing to compensatory keratin expression, the overall contribution of keratins to cell mechanics was difficult to examine in vivo on deletion of single keratin genes. To overcome this problem, we used keratinocytes lacking all keratins. The mechanical properties of these cells were analyzed by atomic force microscopy (AFM) and magnetic tweezers experiments. We found a strong and highly significant softening of keratin-deficient keratinocytes when analyzed by AFM on the cell body and above the nucleus. Magnetic tweezers experiments fully confirmed these results showing, in addition, high viscous contributions to magnetic bead displacement in keratin-lacking cells. Keratin loss neither affected actin or microtubule networks nor their overall protein concentration. Furthermore, depolymerization of actin preserves cell softening in the absence of keratin. On reexpression of the sole basal epidermal keratin pair K5/14, the keratin filament network was reestablished, and mechanical properties were restored almost to WT levels in both experimental setups. The data presented here demonstrate the importance of keratin filaments for mechanical resilience of keratinocytes and indicate that expression of a single keratin pair is sufficient for almost complete reconstitution of their mechanical properties.

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“…In fact, 28 type I Ks and 26 type II Ks as components of intermediate filaments (IFs) are known to be expressed in human epithelial cells (appendage-forming epithelia such as inner hair follicles) and structural epithelial cells (hard structures and appendages such as hair, nail and tongue). Moreover, Ks are differentially expressed as specific pairs of type I (smaller and relatively acidic, 40-63 kDa and pI 4.5-5.5) and type II (larger and more basic, 53-67 kDa and pI 4.5-7.5) proteins, both of which are necessary for filament formation: at least one pair of Ks is always expressed in every epithelial cell (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of keratins 8, 18 and 19 influences invasiveness of human cultured squamous cell carcinoma and adenocarcinoma cells

Uchiumi

Yamashita

Katagata

2011

Experimental and Therapeutic Medicine

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Abstract. Keratin (K) expression index has been reported to be related to cell invasion activity in adenocarcinoma. In a previous study, we observed a negative correlation between K expression and cell invasion activity; i.e., when many Ks are expressed in the cells, the cell activity is low. To further elucidate the correlation between Ks and invasion activity, RNA interference experiments of K8, K18 and K19 were carried out to clarify the essential role of Ks using T24 and HEC-1 as typical squamous cell carcinoma and adenocarcinoma cells, respectively. K8 small interfering RNA (siRNA) was most effective against K18 and K19 expression and demonstrated the strongest effect on relative invasion activity among the siRNAs used. These results suggest that K8/K18 or K8/K19 filaments may play roles in internal cell structure and invasion activity. Moreover, K18 and K19 were capable of substituting for each other, and K18 or K19 formed filaments with K8. In addition, cells treated with K8 siRNA demonstrated high invasion activity, which was approximately double that observed with control siRNA in HEC-1 cells. The order of effects was K8>K19>K18 in the two cell lines. The above results suggest that K8 may play a signifiant role in invasive functions in epithelial and metastatic cells. IntroductionAs inferred from the developmental origins of epithelial tissues, keratins (Ks) may be expressed in adenocarcinoma and urinary bladder carcinoma, as well as in squamous cell carcinoma (SCC). In fact, 28 type I Ks and 26 type II Ks as components of intermediate filaments (IFs) are known to be expressed in human epithelial cells (appendage-forming epithelia such as inner hair follicles) and structural epithelial cells (hard structures and appendages such as hair, nail and tongue). Moreover, Ks are differentially expressed as specific pairs of type I (smaller and relatively acidic, 40-63 kDa and pI 4.5-5.5) and type II (larger and more basic, 53-67 kDa and pI 4.5-7.5) proteins, both of which are necessary for filament formation: at least one pair of Ks is always expressed in every epithelial cell (1-3).The type-specific distribution of IF protein has been increasingly used as the basis for the differential histopathological diagnosis of tumors where morphological criteria have proven to be inconclusive. It has been reported that Ks are expressed in epidermal melanocytes derived from neural crest cells and neural ectoderm (4,5). The evidence presented above suggests that K expression may be related to further differentiation in epithelial tissues, and is not derived from original cells or tissues.In a previous study, we observed a negative correlation between K expression (the number of Ks expressed) and cell invasion capability in three cultured human adenocarcinoma cell lines (6). The number of expressed Ks increases inversely with the invasive index as follows: SW-13 (7) (K number, 2.5; invasion index, 1.781), RERF-LC-OK (K number, 6.5; invasion index, 1.219), and HEC-1 (8) (K number, 7.5; invasion index, 0.562). That is, the nu...

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Structural and regulatory functions of keratins

Cited by 270 publications

References 127 publications

Mechanisms for the formation of membranous nanostructures in cell-to-cell communication

Mechanisms for the formation of membranous nanostructures in cell-to-cell communication

Keratins as the main component for the mechanical integrity of keratinocytes

Downregulation of keratins 8, 18 and 19 influences invasiveness of human cultured squamous cell carcinoma and adenocarcinoma cells

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