The stratified skin epidermis needs dynamic cell rearrangement to self-renew while maintaining tissue integrity to guarantee barrier function in the face of continuous mechanical stress. The contractile actomyosin cytoskeleton connects with intercellular adheres junctions to enable cellular rearrangements and migration, whereas the physical properties of the keratin intermediate filament cytoskeleton through its interaction with intercellular desmosomes mechanically strengthen tissues. How cells coordinate resilience and cellular reorganization to maintain tissue integrity during renewal while adapting to mechanical stress is not known. We show that the polarity kinase aPKC balances keratin- and actin-linked cell-cell and cell-matrix stresses to coordinate basal to suprabasal movement. We find that loss of aPKC promotes resilience of stratified sheets, independent of its regulation of desmosomes. Instead, loss of aPKC promotes a more filamentous stressed keratin network. This change is accompanied by increased contractility and an inability to reorganize F-actin stress fibers into cortical F-actin. Importantly, inhibiting contractility reverses keratin organization and lowered resilience upon loss of aPKC. Increasing actomyosin contractility in control keratinocytes was sufficient to increase stressed keratins and resilience, suggesting that keratins respond to tissue prestress. In conclusion, our data suggest that aPKC serves as a mechanical rheostat that adapts actomyosin activity to control suprabasal keratin organization and tissue resilience.

ESDR185 - aPKC is a rheostat that controls basal junctional dynamics and suprabasal cytoskeletal organization essential for epidermal dynamics and integrity

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.