Critical Reviews in Oral Biology & Medicine, Vol 11, 383-408, Copyright © 2000 by International & American Associations for Dental Research
Epithelial structural proteins of the skin and oral cavity: function in health and disease
R. B. Presland and B. A. Dale
Department of Oral Biology, University of Washington, Seattle 98195, USA. rp@u.washington.edu
Epithelial tissues function to protect the organism from physical,
chemical, and microbial damage and are essential for survival. To perform
this role, epithelial keratinocytes undergo a well-defined differentiation
program that results in the expression of structural proteins which
maintain the integrity of epithelial tissues and function as a protective
barrier. This review focuses on structural proteins of the epidermis and
oral mucosa. Keratin proteins comprise the predominant cytoskeletal
component of these epithelia. Keratin filaments are attached to the plasma
membrane via desmosomes, and together these structural components form a
three-dimensional array within the cytoplasm of epithelial cells and
tissues. Desmosomes contain two types of transmembrane proteins, the
desmogleins and desmocollins, that are members of the cadherin family. The
desmosomal cadherins are linked to the keratin cytoskeleton via several
cytoplasmic plaque proteins, including desmoplakin and plakoglobin
(gamma-catenin). Epidermal and oral keratinocytes express additional
differentiation markers, including filaggrin and trichohyalin, that
associate with the keratin cytoskeleton during terminal differentiation,
and proteins such as loricrin, small proline-rich proteins, and involucrin,
that are cross-linked into the cornified envelope by transglutaminase
enzymes. The importance of these cellular structures is highlighted by the
large numbers of genetic and acquired (autoimmune) human disorders that
involve mutations in, or autoantibodies to, keratins and desmosomal and
cornified envelope proteins. While much progress has been made in the
identification of the structural proteins and enzymes involved in
epithelial differentiation, regulation of this process is less clear. Both
calcium and retinoids influence epithelial differentiation by altering the
transcription of target genes and by regulating activity of enzymes
critical in epithelial differentiation, such as transglutaminases,
proteinases, and protein kinases. These studies have furthered our
understanding of how epithelial tissue and cell integrity is maintained and
provide a basis for the future treatment of skin and oral disorders by gene
therapy and other novel therapeutics.
