Abstract
Keratin intermediate filaments form strong mechanical scaffolds that confer structural stability to epithelial tissues, but the reason this function requires a protein family with 54 isoforms is not understood. During skin wound healing, a shift in keratin isoform expression alters the composition of keratin filaments. How this change modulates cellular function to support epidermal remodeling remains unclear. We report an unexpected effect of keratin isoform variation on kinase signal transduction. Increased expression of wound-associated keratin 6A, but not of steady-state keratin 5, potentiated keratinocyte migration and wound closure without compromising epidermal stability by activating myosin motors. This pathway depended on isoform-specific interaction between intrinsically disordered keratin head domains and non-filamentous vimentin shuttling myosin-activating kinases. These results substantially expand the functional repertoire of intermediate filaments from their canonical role as mechanical scaffolds to include roles as isoform-tuned signaling scaffolds that organize signal transduction cascades in space and time to influence epithelial cell state.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Additional data characterizing the interaction between non-filamentous vimentin and keratin filaments in-vitro, characterizing non-filamentous vimentin in keratinocytes and skin tissue, controlling for potential off-target effects of protein tags and shRNA constructs, verifying sensitivity of the mechanical fragmentation assay, and illustrating the image analysis pipelines.
