Hemidesmosome-Related Keratin Filament Bundling and Nucleation

Abstract

The epithelial cytoskeleton encompasses actin filaments, microtubules, and keratin intermediate filaments. They are interconnected and attached to the extracellular matrix via focal adhesions and hemidesmosomes. To study their interplay, we inhibited actin and tubulin polymerization in the human keratinocyte cell line HaCaT by latrunculin B and nocodazole, respectively. Using immunocytochemistry and time-lapse imaging of living cells, we found that inhibition of actin and tubulin polymerization alone or in combination induced keratin network re-organization albeit differently in each situation. Keratin filament network retraction towards the nucleus and formation of bundled and radial keratin filaments was most pronounced in latrunculin-B treated cells but less in doubly-treated cells and not detectable in the presence of nocodazole alone. Hemidesmosomal keratin filament anchorage was maintained in each instance, whereas focal adhesions were disassembled in the absence of actin filaments. Simultaneous inhibition of actin and tubulin polymerization, therefore, allowed us to dissect hemidesmosome-specific functions for keratin network properties. These included not only anchorage of keratin filament bundles but also nucleation of keratin filaments, which was also observed in migrating cells. The findings highlight the fundamental role of hemidesmosomal adhesion for keratin network formation and organization independent of other cytoskeletal filaments pointing to a unique mechanobiological function.

The laminin-keratin link shields the nucleus from mechanical deformation and signalling

“…Since integrin β4 binds to the keratin cytoskeleton and to the surrounding substrate, it can be understood as a “docking site” for the keratin network to the substrate 59 . This incorporation will have two effects.…”

Increased Expression of Flightless I in Cutaneous Squamous Cell Carcinoma Affects Wnt/β-Catenin Signaling Pathway

“…Talin has also been identified as the most highly expressed integrin-cytoskeleton crosslinker that promotes integrin activation and is associated with increased invasion of cSCC into the adjacent tissue [35]. Talin has also been shown to affect hemidesmosomal-like anchorage of keratinocytes and influence keratin network organization, including keratin filament bundling and nucleation in epithelial cancer cells [43]. Data presented here suggest that Flii may increase talin expression in cSCC to upregulate K14 signaling; however, further research is required to understand the exact mechanism.…”

A Flexible and Moisturizing Multilayer Microporous Sponge Copolymerized with Keratin and Alginate

“…[14] Moreover, after moderate modification, keratin could be applied in clinical use, [15,16] which is divided into cytoskeleton intermediate filament protein. [17,18] It was also found that the mixing of keratin and chitosan could significantly enhance the formation of blood vessels to achieve the effect of nerve repair. [19] As we know, most of the feather keratin (FK) were discarded, resulting in waste of resources and environmental pollution.…”

“…Due to its excellent biocompatibility, it can be used to prepare keratin membranes, [11,12] nanoparticle scaffolds [13] or pH‐sensitive hydrogen [14] . Moreover, after moderate modification, keratin could be applied in clinical use, [15,16] which is divided into cytoskeleton intermediate filament protein [17,18] . It was also found that the mixing of keratin and chitosan could significantly enhance the formation of blood vessels to achieve the effect of nerve repair [19] …”