A matricellular protein fibulin-4 is essential for the activation of lysyl oxidase
In: Science advances, Jg. 6 (2020-04-08), Heft 48
Online
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Zugriff:
A secreted protein activates a major extracellular matrix cross-linking enzyme by promoting copper ion transfer in the Golgi.
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.
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A matricellular protein fibulin-4 is essential for the activation of lysyl oxidase
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Autor/in / Beteiligte Person: | Noda, Kazuo ; Nakamura, Tomoyuki ; Akama, Tomoya O. ; Yamauchi, Mitsuo ; Horiguchi, Masahito ; Miki, Takao ; Kitagawa, Kaori ; Terajima, Masahiko ; Takahashi, Kazuaki ; Ogra, Yasumitsu ; Taniguchi, Hisaaki ; Mecham, Robert P. ; Taniguchi, Takako |
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Zeitschrift: | Science advances, Jg. 6 (2020-04-08), Heft 48 |
Veröffentlichung: | 2020 |
Medientyp: | unknown |
ISSN: | 2375-2548 (print) |
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