| First Author | Noda K | Year | 2020 |
| Journal | Sci Adv | Volume | 6 |
| Issue | 48 | PubMed ID | 33239290 |
| Mgi Jnum | J:313480 | Mgi Id | MGI:6800555 |
| Doi | 10.1126/sciadv.abc1404 | Citation | Noda K, et al. (2020) A matricellular protein fibulin-4 is essential for the activation of lysyl oxidase. Sci Adv 6(48) |
| abstractText | Fibulin-4 is a matricellular protein required for extracellular matrix (ECM) assembly. Mice deficient in fibulin-4 (Fbln4(-/-) ) have disrupted collagen and elastin fibers and die shortly after birth from aortic and diaphragmatic rupture. The function of fibulin-4 in ECM assembly, however, remains elusive. Here, we show that fibulin-4 is required for the activity of lysyl oxidase (LOX), a copper-containing enzyme that catalyzes the covalent cross-linking of elastin and collagen. LOX produced by Fbln4(-/-) cells had lower activity than LOX produced by wild-type cells due to the absence of lysine tyrosyl quinone (LTQ), a unique cofactor required for LOX activity. Our studies showed that fibulin-4 is required for copper ion transfer from the copper transporter ATP7A to LOX in the trans-Golgi network (TGN), which is a necessary step for LTQ formation. These results uncover a pivotal role for fibulin-4 in the activation of LOX and, hence, in ECM assembly. |
