The nature and significance of differential keratin gene expression.

Keratin filaments are 8 nm in diameter, and together with the 6 nm actin microfilaments and the 23 nm microtubules, they constitute the cytoskeletal architecture of most vertebrate epithelial The filaments are assembled from two classes of subunits, type I and type II.12.13-16 The type I keratins are acidic and generally small in size (40-57 kD). The type I1 keratins are more basic and larger in size (53-67 kD).’lslz Each class is encoded by a small multigene family,1zs15 the members of which are differentially expressed in different epithelial ce11s,10*11*17-20 at different stages of differentiation and de~eloprnent,6.~~~~’-~~ and upon malignant transformation?”** At any given time, an epithelial cell typically expresses two to five keratin polypeptides, including at least one member of each type.’2.15,20,29 Prior to the discovery of the two distinct types of keratin subunits and their coordinate expression, it was shown that no single keratin protein of either type by itself was competent for filament assembly.3s32 Collectively, these results suggest that the expression of both types may be essential for subsequent filament formation. The details of how the keratin subunits assemble remain to be elucidated. Until recently, most of what we knew about the structure of the keratin filament came from the early X-ray diffraction studies of Crick and Pauling back in the early 1950~.’~.’~ The 8 nm keratin filament was known to be made up of an as yet undetermined number of smaller, closely packed filaments, called protofilaments. Each protofilament has a diameter of about 2 nm and is itself made up of several a-helical polypeptide strands intertwined in a coiled-coil configuration. The early X-ray studies could not decipher whether two or three helical polypeptide subunits were interwoven to give the coiled-coil substructure of the protofilament. Although physicochemical studies suggested a three-stranded coiled ~oil:~.’~ model