KERATIN REMODELING IN STRESS

Abstract

Remodeling of keratin cytoskeletal network is essential for cells to respond to environmental cues. To understand the stress/wound response, immortalized keratinocytes are used which expressed a keratin mutation mimicking severe EBS Dowling-Meara (a skin fragility disorder), fluorescently tagged for live-cell imaging.

All keratinocytes are ¿activated¿ to a stress state through up-regulation of kinases and wound response proteins, but revert to quiescence after confluence. In mutant cells, ¿activation¿ is reflected by the presence of keratin aggregates, a hallmark of severe EBS-DM. It is thought that avoiding aggregate formation may improve the disease phenotype.

It is observed that EGF influences keratin aggregate formation/dynamics in mutant keratinocytes, through changes in plectin expression, during cell migration. Phosphorylation at K14 Y129 is found to play a role in keratin aggregate formation, modulating cell migration during scratch wound assays.

This thesis demonstrates how plasticity of the keratin cytoskeleton can modulate the skin cell¿s response to environmental cues.