| First Author | Yamamoto-Tanaka M | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 29 | Pages | 20026-38 |
| PubMed ID | 24872419 | Mgi Jnum | J:216017 |
| Mgi Id | MGI:5607491 | Doi | 10.1074/jbc.M113.543421 |
| Citation | Yamamoto-Tanaka M, et al. (2014) Mesotrypsin and caspase-14 participate in prosaposin processing: potential relevance to epidermal permeability barrier formation. J Biol Chem 289(29):20026-38 |
| abstractText | A proteomics-based search for molecules interacting with caspase-14 identified prosaposin and epidermal mesotrypsin as candidates. Prosaposin is a precursor of four sphingolipid activator proteins (saposins A-D) that are essential for lysosomal hydrolysis of sphingolipids. Thus, we hypothesized that caspase-14 and mesotrypsin participate in processing of prosaposin. Because we identified a saposin A sequence as an interactor with these proteases, we prepared a specific antibody to saposin A and focused on saposin A-related physiological reactions. We found that mesotrypsin generated saposins A-D from prosaposin, and mature caspase-14 contributed to this process by activating mesotrypsinogen to mesotrypsin. Knockdown of these proteases markedly down-regulated saposin A synthesis in skin equivalent models. Saposin A was localized in granular cells, whereas prosaposin was present in the upper layer of human epidermis. The proximity ligation assay confirmed interaction between prosaposin, caspase-14, and mesotrypsin in the granular layer. Oil Red staining showed that the lipid envelope was significantly reduced in the cornified layer of skin from saposin A-deficient mice. Ultrastructural studies revealed severely disorganized cornified layer structure in both prosaposin- and saposin A-deficient mice. Overall, our results indicate that epidermal mesotrypsin and caspase-14 work cooperatively in prosaposin processing. We propose that they thereby contribute to permeability barrier formation in vivo. |
