ABSTRACT
Among all cytoskeletal proteins, keratins have evolved into the most divergent group in mammals, reflecting the functional needs of diverse epithelial cell types and tissues. The assembly and regulation of the actin and the microtubule cytoskeleton, and their predominant function in cell adhesion, polarity, intracellular transport, migration, and cell division are relatively well known. The subcellular architecture and the celland tissue-specific function of 6 human actins and 13 a-and b-tubulins is mainly regulated by a very large number of well-characterized associated protein families. This does not appear to be the case for keratins, for which only a very limited number of bona fide associated proteins, mainly plakins and cornified envelope proteins, are presently known (1,2). These provide membrane attachment sites and mediate the transient interaction of keratins with the actin and the microtubule cytoskeleton. The prevailing principle responsible for tissue-specific keratin function and regulation appears to result from the transcriptional regulation of their genes and the intrinsic property of the >50 different protein sequences. The former gives rise to exquisite, cell type-specific keratin profiles, which are responsible for the micromechanical properties of epithelial cells and their distinct cytoskeletal architecture. The latter has endowed them with distinct assembly properties and half-life times, and provides unique target sites for a large number of kinases and phosphatases (1,3). These principles govern the scaffolding function of keratins, which is their predominant function as underscored by keratinopathies (4-6) and experiments in knockout mice (1,2,7,8).
