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Functional differences between keratins of stratified and simple epithelia
E Hutton1, R D Paladini, Q C Yu
1Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA.
The Journal of Cell Biology
|October 24, 1998
Summary
Different keratins have unique functions. A hybrid epidermal keratin fully restored skin integrity in mice lacking keratin 14, while simple epithelial keratin 18 only partially rescued the phenotype, indicating keratins are not interchangeable.
Area of Science:
- Cell Biology
- Biochemistry
- Dermatology
Background:
- Stratified and simple epithelial tissues express distinct keratin pairs (K5/K14 and K8/K18, respectively).
- Keratins are hypothesized to provide mechanical integrity to epithelial cells, as their absence causes blistering and hemorrhaging.
- The functional specificity of different keratins in vivo remains an open question.
Observation:
- Transgenic mice lacking keratin 14 (K14 null) were used to investigate keratin function.
- A K16-14 hybrid epidermal keratin transgene and a K18 simple epithelial keratin transgene were expressed in the epidermis of K14 null mice.
- The ability of K18 to form filaments with K5 in vitro and in vivo was assessed.
Findings:
- The K16-14 hybrid keratin fully restored a wild-type phenotype to the newborn epidermis.
- Keratin 18 partially rescued the K14 null phenotype, but was insufficient to fully restore skin integrity.
- The K5/K18 keratin network, while forming filaments, was deficient in mechanical stress resistance, leading to skin perturbations under mechanical stress.
Implications:
- The functional compensation between different keratin types is incomplete.
- Simple epithelial keratins (like K18) cannot fully substitute for epidermal keratins (like K14) in maintaining skin integrity.
- These findings demonstrate that different keratins have non-equivalent, specific functions in vivo, particularly concerning mechanical resilience.