776 A keratin switch promotes epidermal remodeling by organizing actomyosin-activating signals

Epidermal stability depends on keratin intermediate filaments, which form a trans-cellular mechanical scaffold. During epidermal remodeling, filament composition shifts, with increased expression of five wound-associated isoforms. However, the function keratins during remodeling remains unclear. Identifying isoform-specific functions has been challenging, since depleting individual compromises more general scaffold function. To disentangle these effects, we take gain-of-function rather than loss-of-function approach. We find that increasing 6A (K6A), but not steady-state K5, promotes keratinocyte migration, especially in stratified cultures. Using live imaging and traction force microscopy, show that, alter scaffold, K6A triggers signaling crosstalk actomyosin to increase generation. Unexpectedly, contractility through preferential interaction between unstructured head domain small pool non-filamentous vimentin. K6A-enriched filaments vimentin anchor transient complex spatially organizing myosin subunits regulatory kinases activate myosin. These results expand functional repertoire beyond their canonical role as scaffolds include scaffolds, activity tuned by specific isoforms expressed.