Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo
Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo
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DOI：
10.1038/415168a
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发表时间：
2002-01-10
期刊：
影响因子：
64.8
通讯作者：
Olson, EN
中科院分区：
文献类型：
--
作者：
Yanagisawa, H;Davis, EC;Olson, EN
细胞外弹性纤维为组织提供机械弹性，并通过影响细胞-细胞信号传递促进器官重建过程(1，2)。弹性纤维的形成需要原弹性蛋白单体的组装和交联，以及由此产生的不可溶弹性蛋白基质组织成功能纤维。参与这一过程的分子和机制尚不清楚。FiBulin-5(又称EVEC/DISAT)是一种细胞外基质蛋白，在胚胎发育过程中广泛表达于大血管和心脏瓣膜，在许多成人组织中都有表达，包括主动脉、肺、子宫和皮肤，这些组织都含有丰富的弹性纤维(3，4)。在这里，我们发现纤维蛋白-5是一种钙依赖的弹性蛋白结合蛋白，在体内定位于弹性纤维的表面。纤维蛋白-5(-/-)小鼠由于弹力纤维组织紊乱而发生明显的弹力性病变，导致皮肤松弛、血管异常和肺气肿。这种表型类似于人类的皮肤松弛综合征，揭示了纤蛋白-5作为组织弹性纤维并将其与细胞联系起来的支架蛋白的关键功能。这种作用可能是由纤毛蛋白-5中的RGD基序和钙离子结合的表皮生长因子(EGF)重复序列和弹性蛋白所介导的，前者与细胞表面整合素结合。
Extracellular elastic fibres provide mechanical elasticity to tissues and contribute towards the processes of organ remodelling by affecting cell-cell signalling(1,2). The formation of elastic fibres requires the assembly and crosslinking of tropoelastin monomers, and organization of the resulting insoluble elastin matrix into functional fibres. The molecules and mechanisms involved in this process are unknown. Fibulin-5 (also known as EVEC/DANCE) is an extracellular matrix protein abundantly expressed in great vessels and cardiac valves during embryogenesis, and in many adult tissues including the aorta, lung, uterus and skin, all of which contain abundant elastic fibres(3,4). Here we show that fibulin-5 is a calcium-dependent, elastin-binding protein that localizes to the surface of elastic fibres in vivo. fibulin-5(-/-) mice develop marked elastinopathy owing to the disorganization of elastic fibres, with resulting loose skin, vascular abnormalities and emphysematous lung. This phenotype, which resembles the cutis laxa syndrome in humans(5), reveals a critical function for fibulin-5 as a scaffold protein that organizes and links elastic fibres to cells. This function may be mediated by the RGD motif in fibulin-5, which binds to cell surface integrins, and the Ca2+-binding epidermal growth factor (EGF) repeats, which bind elastin.