Focal adhesions are hotspots for keratin filament precursor formation

Windoffer, Reinhard; Kölsch, Anne; Wöll, Stefan; Leube, Rudolf E.

doi:10.1083/jcb.200511124

Cited by 87 publications

(111 citation statements)

References 28 publications

(50 reference statements)

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“…1C, arrowhead), and may be related to the presence of hemidesmosomes [40]. Alternatively, it has been shown that focal adhesions may act polymerizing keratin IFs [41]. It is difficult to conceive how this mechanism may be related to the bulk of the apical IFs, but it may be related to the small basal population of IFs.…”

Section: Location Location Location: Apical Distribution Of Intermementioning

confidence: 98%

Intermediate filaments: A role in epithelial polarity

Oriolo

Wald

Palau

et al. 2007

Experimental Cell Research

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Intermediate filaments have long been considered mechanical components of the cell that provide resistance to deformation stress. Practical experimental problems, including insolubility, lack of good pharmacological antagonists, and the paucity of powerful genetic models, have handicapped the research of other functions. In single-layered epithelial cells, keratin intermediate filaments are cortical, either apically polarized or apico-lateral. This review analyzes phenotypes of genetic manipulations of simple epithelial cell keratins in mice and C. elegans that strongly suggest a role of keratins in apico-basal polarization and membrane traffic. Published evidence that intermediate filaments can act as scaffolds for proteins involved in membrane traffic and signaling is also discussed. Such a scaffolding function would generate a highly polarized compartment within the cytoplasm of simple epithelial cells. While in most cases mechanistic explanations for the keratinnull or overexpression phenotypes are still missing, it is hoped investigators will be encouraged to study these as yet poorly understood functions of intermediate filaments.

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Section: Location Location Location: Apical Distribution Of Intermementioning

confidence: 98%

Intermediate filaments: A role in epithelial polarity

Oriolo

Wald

Palau

et al. 2007

Experimental Cell Research

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“…1 and Fig. 5B; supplementary material Movies 1, 2, 8) ( Windoffer et al, 2006;Yoon et al, 2001). Cells with increased KF-network reorganization, such as migrating cells, show a considerable increase in KFP formation ( Fig.…”

Section: Nucleationmentioning

confidence: 99%

“…1) (Windoffer et al, 2006;Woll et al, 2005). Focal adhesions are important regulators of keratin nucleation (Windoffer et al, 2006) by direct and/or indirect molecular association [ (Steinbock et al, 2000); for other IFs, see the following references (Kreis et al, 2005;Nikolic et al, 1996;Spurny et al, 2008;Steinbock et al, 2000;Sun et al, 2008a;Sun et al, 2008b;Tsuruta and Jones, 2003)] and/or by signalling (e.g. Omary et al, 1998;Woll et al, 2007).…”

Section: Nucleationmentioning

confidence: 99%

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The keratin-filament cycle of assembly and disassembly

Kölsch

Windoffer

Würflinger

et al. 2010

Journal of Cell Science

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104

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Continuous and regulated remodelling of the cytoskeleton is crucial for many basic cell functions. In contrast to actin filaments and microtubules, it is not understood how this is accomplished for the third major cytoskeletal filament system, which consists of intermediate-filament polypeptides. Using time-lapse fluorescence microscopy of living interphase cells, in combination with photobleaching, photoactivation and quantitative fluorescence measurements, we observed that epithelial keratin intermediate filaments constantly release non-filamentous subunits, which are reused in the cell periphery for filament assembly. This cycle is independent of protein biosynthesis. The different stages of the cycle occur in defined cellular subdomains: assembly takes place in the cell periphery and newly formed filaments are constantly transported toward the perinuclear region while disassembly occurs, giving rise to diffusible subunits for another round of peripheral assembly. Remaining juxtanuclear filaments stabilize and encage the nucleus. Our data suggest that the keratin-filament cycle of assembly and disassembly is a major mechanism of intermediate-filament network plasticity, allowing rapid adaptation to specific requirements, notably in migrating cells.

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“…Additionally, there is precedence for FAs being important for IF organization (Bhattacharya et al, 2009;Burgstaller et al, 2010;Windoffer et al, 2006). Thus, we next determined if the plectincontaining cFAs influence the distribution of the IF keratin cytoskeleton of rAEC (Eisenberg et al, 2011;Takawira et al, 2011).…”

Section: Fa Double Ring Formation Is Plectin Dependentmentioning

confidence: 99%

Plectin-containing, centrally-localized focal adhesions exert traction forces in primary lung epithelial cells

Eisenberg

Beaumont

Takawira

et al. 2013

Journal of Cell Science

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SummaryReceptor clustering upon cell attachment to the substrate induces assembly of cytoplasmic protein complexes termed focal adhesions (FAs), which connect, albeit indirectly, the extracellular matrix to the cytoskeleton. A subset of cultured primary alveolar epithelial cells (AEC) display a unique pattern of vinculin/paxillin/talin-rich FAs in two concentric circles when cultured on glass and micropatterned substrates: one ring of FAs located at the cell periphery (pFAs), and another FA ring located centrally in the cell (cFAs). Unusually, cFAs associate with an aster-like actin array as well as keratin bundles. Moreover, cFAs show rapid paxillin turnover rates following fluorescence recovery after photobleaching and exert traction forces similar to those generated by FAs at the cell periphery. The plakin protein plectin localizes to cFAs and is normally absent from pFAs, whereas tensin, a marker of mature/fibrillar adhesions, is found in both cFAs and pFAs. In primary AEC in which plectin expression is depleted, cFAs are largely absent, with an attendant reorganization of both the keratin and actin cytoskeletons. We suggest that the mechanical environment in the lung gives rise to the assembly of unconventional FAs in AEC. These FAs not only show a distinctive arrangement, but also possess unique compositional and functional properties.

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Focal adhesions are hotspots for keratin filament precursor formation

Cited by 87 publications

References 28 publications

Intermediate filaments: A role in epithelial polarity

Intermediate filaments: A role in epithelial polarity

The keratin-filament cycle of assembly and disassembly

Plectin-containing, centrally-localized focal adhesions exert traction forces in primary lung epithelial cells

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