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© The Rockefeller University Press, 0021-9525/1998//487 $5.00
The Journal of Cell Biology, Volume 143, Number 2, , 1998 487-499

Regular Articles

Functional Differences between Keratins of Stratified and Simple Epithelia



Elizabeth Hutton*, Rudolph D. Paladini{ddagger}, Qian-Chun Yu*, Mei Yen*, Pierre A. Coulombe{ddagger}, and Elaine Fuchs*

* Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637; and {ddagger} Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Dividing populations of stratified and simple epithelial tissues express keratins 5 and 14, and keratins 8 and 18, respectively. It has been suggested that these keratins form a mechanical framework important to cellular integrity, since their absence gives rise to a blistering skin disorder in neonatal epidermis, and hemorrhaging within the embryonic liver. An unresolved fundamental issue is whether different keratins perform unique functions in epithelia. We now address this question using transgenic technology to express a K16-14 hybrid epidermal keratin transgene and a K18 simple epithelial keratin transgene in the epidermis of mice null for K14. Under conditions where the hybrid epidermal keratin restored a wild-type phenotype to newborn epidermis, K18 partially but not fully rescued. The explanation does not appear to reside in an inability of K18 to form 10-nm filaments with K5, which it does in vitro and in vivo. Rather, it appears that the keratin network formed between K5 and K18 is deficient in withstanding mechanical stress, leading to perturbations in the keratin network in regions of the skin that are subjected either to natural or to mechanically induced trauma. Taken together, these findings suggest that the loss of a type I epidermal keratin cannot be fully compensated by its counterpart of simple epithelial cells, and that in vivo, all keratins are not equivalent.

Key Words: keratins • intermediate filaments • functional redundancy • epidermis • epithelia

Abbreviations used in this paper: BS3, bis(sulfosuccinimidyl)suberate; EBS, epidermis bullosa simplex; IF, intermediate filament.

A special thank you goes to L. Degenstein for her help in transgenic mice aspects of this work, and in conducting the mouse skin rubbing experiments. We thank D. Dugger for technical assistance in transgenic mouse engineering; G. Strasser and D. Lourim for technical assistance in some phases of the cell and molecular biology; Dr. C. Bauer for his expert assistance in electron microscopy and in assisting with some of the photography and figure preparations; E. Smith and C. Wellek for their help with the computer-assisted art work; J. Fradette (University Laval, Quebec, Canada) for providing the chemical cross-linking data; Dr. M.B. Omary (Stanford University, Palo Alto, CA) for providing the pET-K18 bacterial expression clone; and Dr. D. Roop (Baylor University School of Medicine) for his gift of anti-K6 antiserum.

Address all correspondence to Elaine Fuchs, Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, 5841 S. Maryland Avenue, Room N314, MC1028, Chicago, IL 60637. Tel.: (773) 702-1347. Fax: (773) 702-0141.


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