Biochemical evidence that small proline-rich proteins and trichohyalin function in epithelia by modulation of the biomechanical properties of their cornified cell envelopes.
The cornified cell envelope (CE) is a specialized structure involved in barrier function in stratified squamous epithelia, and is assembled by transglutaminase cross-linking of several proteins. Murine forestomach epithelium undergoes particularly rigorous mechanical trauma, and these CEs contain the highest known content of small proline-rich proteins (SPRs). Sequencing analyses of these CEs revealed that SPRs function as cross-bridgers by joining other proteins by use of multiple adjacent glutamines and lysines on only the amino and carboxyl termini and in functionally non-polar ways. Forestomach CEs also use trichohyalin as a novel cross-bridging protein. We performed mathematical modeling of amino acid compositions of the CEs of mouse and human epidermis of different body sites. Although the sum of loricrin + SPRs was conserved, the amount of SPRs varied in relation to the presumed physical requirements of the tissues. Our data suggest that SPRs could serve as modifiers of a composite CE material composed of mostly loricrin; we propose that increasing amounts of cross-bridging SPRs modify the structure of the CE, just as cross-linking proteins strengthen other types of tissues. In this way, different epithelia may use varying amounts of the cross-bridging SPRs to alter the biomechanical properties of the tissue in accordance with specific physical requirements and functions.
Steinert
P M
PM
Laboratory of Skin Biology, NIAMS, National Institutes of Health, Bethesda, Maryland 20892-2752, USA. pemast@helix.nih.gov
Kartasova
T
T
Marekov
L N
LN
D000595:Amino Acid Sequence; D000818:Animals; D001696:Biomechanical Phenomena; D016764:Cell Polarity; D003001:Cloning, Molecular; D055233:Cornified Envelope Proline-Rich Proteins; D003432:Cross-Linking Reagents; D004848:Epithelium / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides; D055232:Proline-Rich Protein Domains; D011498:Protein Precursors / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism* / Q000502:physiology*; D011817:Rabbits; D013270:Stomach / Q000737:chemistry*
D055233:Cornified Envelope Proline-Rich Proteins; D003432:Cross-Linking Reagents; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D010455:Peptides; D011498:Protein Precursors; D011506:Proteins; C112254:SPRR3 protein, human; C064554:loricrin; C016159:trichohyalin