Genome organization, assembly, and epithelial function of keratins. (A) Arrangement of keratin clusters in the mouse genome. Human keratin genes that have not been identified or annotated in the mouse genome are shown on the bottom side and marked with a question mark. The arrows mark the boundaries of the region deleted by Vijayaraj et al. (2009) on mouse chromosome 15. (B) Summary of the multistep pathway through which type I and II keratin protein monomers polymerize to form 10-nm filaments. The antiparallel docking of the lollipop-shaped coiled-coiled dimers along their lateral surfaces generates structurally apolar tetramers and accounts for the lack of polarity of assembled keratin intermediate filaments. For all steps in the pathway, the forward (assembly promoting) reaction is heavily favored in vitro (Kim and Coulombe, 2007). (C) Keratins influence the localization and function of many cellular components. As highlighted here, keratins interact with and modulate the mTOR pathway in several ways, both in skin keratinocytes and gut epithelial cells, and regulate the localization of microtubules, γ-tubulin, and GLUT transporters in polarized epithelia. Components are not drawn to scale in this schematic.