Keratin filaments and soluble vimentin interact to organize signal transduction

Summary: Abstract Body: The keratin intermediate filament (IF) cytoskeleton provides crucial mechanical support for the epidermis, but the large number of keratin genes and their context-dependent expression patterns suggest additional non-mechanical roles. How individual IF proteins might perform different non-mechanical functions while maintaining the canonical IF mechanical scaffold has not been clear. We recently found that changing keratin expression during skin wound healing triggers a myosin-activating signaling circuit, potentiating wound closure without compromising mechanical stability. We now report that this signal transduction pathway relies on non-filamentous small oligomers of vimentin, the principal IF protein in mesenchymal cells, to shuttle regulatory kinases into transient signaling complexes with myosin organized on keratin 6A-containing filaments. These results highlight two mechanisms by which IF proteins differentially influence cell signaling and cell mechanics. First, through isoform specific interactions, changing keratin expression modulates recruitment of different proteins to the IF cytoskeleton, increasing the likelihood that these proteins interact. This allows the IF cytoskeleton to spatially and temporally organize signal transduction, effectively functioning as a membraneless organelle. Second, largely overlooked non-filamentous pools of even lowly expressed IF proteins can function as signaling shuttles or adapters. Context-dependent cell and tissue regulation, rather than simple mechanics, may therefore explain the size of the IF protein family. Benjamin A. Nanes¹, Surbhi Chouhan¹, Rajaa Boujemaa-Paterski², Sabahat Munawar¹, Kushal Bhatt¹, Divya Rajendran¹, Tadamoto Isogai¹, Ohad Medalia², Gaudenz Danuser¹ 1. UT Southwestern Medical Center, Dallas, TX, United States. 2. University of Zurich, Zurich, Switzerland. Epidermal Structure and Barrier Function