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 i n barrier function in stratified squamous epithelia, and is assembled by transglutaminase cross-linking of several proteins. Murine forestom ach epithelium undergoes particularly rigorous mechanical trauma, and these CEs contain the highest known content of small proline-rich prot eins (SPRs). Sequencing analyses of these CEs revealed that SPRs funct ion as cross-bridgers by joining other proteins by use of multiple adj acent glutamines and lysines on only the amino and carboxyl termini an d in functionally non-polar ways. Forestomach CEs also use trichohyali n as a novel cross-bridging protein. We performed mathematical modelin g of amino acid compositions of the CEs of mouse and human epidermis o f different body sites. Although the sum of loricrin + SPRs was conser ved, the amount of SPRs varied in relation to the presumed physical re quirements of the tissues. Our data suggest that SPRs could serve as m odifiers of a composite CE material composed of mostly loricrin; we pr opose that increasing amounts of cross-bridging SPRs modify the struct ure of the CE, just as cross-linking proteins strengthen other types o f 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 .