| First Author | Zemskov EA | Year | 2007 |
| Journal | J Cell Sci | Volume | 120 |
| Issue | Pt 18 | Pages | 3188-99 |
| PubMed ID | 17711877 | Mgi Jnum | J:128393 |
| Mgi Id | MGI:3766887 | Doi | 10.1242/jcs.010397 |
| Citation | Zemskov EA, et al. (2007) Cell-surface transglutaminase undergoes internalization and lysosomal degradation: an essential role for LRP1. J Cell Sci 120(Pt 18):3188-99 |
| abstractText | Tissue transglutaminase functions as a protein crosslinking enzyme and an integrin-binding adhesion co-receptor for fibronectin on the cell surface. These activities of transglutaminase and the involvement of this protein in cell-matrix adhesion, integrin-mediated signaling, cell migration and matrix organization suggest a precise and efficient control of its cell-surface expression. We report a novel mechanism of regulation of surface transglutaminase through internalization and subsequent lysosomal degradation. Constitutive endocytosis of cell-surface transglutaminase depends on plasma membrane cholesterol and the activity of dynamin-2, and involves both clathrin-coated pits and lipid rafts or caveolae. Furthermore, the key matrix ligands of transglutaminase, fibronectin and platelet-derived growth factor, promote its endocytosis from the cell surface. Our results also indicate that transglutaminase interacts in vitro and on the cell surface with the major endocytic receptor, low-density lipoprotein receptor-related protein 1, and demonstrate the requirement for this receptor in the endocytosis of transglutaminase. Finally, a deficiency of this endocytic receptor or blockade of endo-lysosomal function upregulate transglutaminase expression on the cell surface, leading to increased cell adhesion and matrix crosslinking. These findings characterize a previously unknown pathway of transglutaminase internalization and degradation that might be crucial for regulation of its adhesive and signaling functions on the cell surface and reveal a novel functional link between cell-matrix adhesion and endocytosis. |
