Expression of unusually large keratins during terminal differentiation: balance of type I and type II keratins is not disrupted.

Abstract

When a basal epidermal cell undergoes a commitment to terminally differentiate, it ceases to divide and begins to migrate outward towards the surface of the skin. Dramatic changes in its cytoskeletal architecture take place, accompanied by numerous changes in the expression of keratins, a family of related polypeptides that form 8-nm filaments in these cells. We show here that a shift to the synthesis of unusually large keratins occurs that does not seem to disrupt the ratio of two distinct subfamilies of keratins. Preliminary studies indicate that this differentiation-specific shift may be at the level of transcriptional rather than post-trancriptional regulation. The striking similarities between these large keratins and the type I and type II keratins of basal epidermal cells suggests the important role that both classes of large keratin sequences must play in the assembly of the intermediate filaments within the differentiating keratinocyte.Several laboratories have reported differences between the keratins of stratum corneum and those of the living layers of epidermis (1--4). During the course of terminal differentiation, changes occur in the expression of the keratin polypeptides that comprise the 8-nm tonofilaments (5-10). For the human, keratins of size 46, 48.5, 50, 52, 56, and 58 kd are synthesized by the basal epidermal cells (Fig. 1, lane 1), whereas additional keratins of size 67, 65.5, and 56.5 kd are produced by the terminally differentiating epidermis (lane 3). As the cells pass through the granular layer to the stratum corneum, a slight reduction in the size of the keratins takes place. As judged by in vitro translation of mRNAs isolated from basal (lane 2) and differentiating (lane 4) keratinocytes, the changes in keratin pattern that occur early in the course of terminal differentiation are clearly at the level of mRNA biosynthesis (5).Recently, it was demonstrated that the keratins produced by basal epidermal cells can be divided into two distinct groups based on the ability of their mRNAs to cross-hybridize with two different cloned keratin cDNAs (11). Other epithelia express different subsets of keratins, but most if not all of these seem to be similar to one or the other of the two epidermal keratin subfamilies (12). The small (40-52 kd) and relatively acidic keratins have been named the type I class, and the large (53-58 kd) and more basic keratins have been named the type II class (13,14). At least one member of each of the two keratin types seem to be expressed in all cells at all times, suggesting their combined importance in filament assembly (14). Sequence analyses (13,(15)(16)(17)(18) have shown that while the two types of keratins share only low (<30%) homology, their predicted secondary structures are strikingly similar and are compatible with their playing an essential role in forming the coiled-coil backbone of the protofilament of the 8-nm keratin filament (13,18).The keratins typical of terminally differentiating keratinocytes seem to be unusually large and are not fo...

Cytokeratin 8: The Dominant Type II Intermediate Filament Protein in Lung Cancer

“…Roughly equimolar amounts of type I and type II CKs are expressed in these cells (Fig. 2, A), which is consistent with previous observations (Kim et al, 1984). In this simplistic model, we regarded CKs as being in a filament form (i.e., insoluble), although a small fraction (~5%) of the total CK has been reported to be soluble (Chou et al, 1993).…”

Structure of a gene for the human epidermal 67-kDa keratin.

“…To our knowledge, the only IF protein gene that has been characterized is that for hamster vimentin (15), but despite the paucity of information, it is nevertheless interesting to compare the exon/intron structure of this keratin and that of vimentin. ------A-----I 503 528 (39) have suggested that the mRNA for the human 67-kDa type II keratin is 3.8 kb long, based on blot analysis with a nonspecific type II cDNA clone. The complete structure of this gene, reported here, shows that its mRNA is actually about 2.5 kb long.…”

Changes in Keratin 6 and Keratin 10 (Co-)Expression in Lesional and Symptomless Skin of Spreading Psoriasis

“…K1 and K10 are markers for differentiation and are only expressed in well-differentiated, suprabasal cells [1, 2]. K6/K16 is a keratin pair which is expressed in hyperproliferative cells and it is also found suprabasally [3, 4]. There is experimental evidence that in psoriasis the keratin K1/K10 pair is down-regulated when expression of the keratin K6/K16 pair is induced [5, 6], a relationship which has also been described for other skin conditions [7, 8].…”