membrane substrates of gingipains

Porphyromonas gingivalis secretes cysteine proteases named gingipains which can cleave an array of proteins and importantly contribute to the development of periodontitis. In this study we focused on gingipain-exerted proteolysis at the cell surface of human gingival epithelial cells (telomerase immortalized gingival keratinocytes [TIGK]). We examined whether gingipains have sheddase activity or if their main activity is degradation of membrane proteins into small fragments. Using mass spectrometry, we investigated the whole sheddome/degradome of TIGK cell surface proteins by P. gingivalis strains differing in gingipain expression. We observed extensive degradation of TIGK surface proteins, suggesting that gingipains could in fact be the major cause of damage to the gingival epithelium. Most of the identified gingipain substrates were molecules involved in adhesion, suggesting that gingipains may cause tissue damage through cleavage of cell contacts, resulting in cell detachment and rounding, and consequently leading to anoikis. These results reveal a molecular underpinning to P. gingivalis-induced tissue destruction and enhance our knowledge of the role of P. gingivalis’ proteases in the pathobiology of periodontitis.