Differential regulation of elastic fiber formation by fibulin-4 and -5.
Differential regulation of elastic fiber formation by fibulin-4 and -5.
复制标题
fibulin-4 和-5 对弹性纤维形成的差异调节。
DOI：
10.1074/jbc.m109.019364
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发表时间：
2009-09-04
影响因子：
4.8
通讯作者：
Kielty, Cay M.
中科院分区：
文献类型：
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作者：
Choudhury, Rawshan;McGovern, Amanda;Ridley, Caroline;Cain, Stuart A.;Baldwin, Andrew;Wang, Ming-Chuan;Guo, Chun;Mironov, Aleksandr, Jr.;Drymoussi, Zoe;Trump, Dorothy;Shuttleworth, Adrian;Baldock, Clair;Kielty, Cay M.
Fibulin-4和Fibulin-5是细胞外糖蛋白，在弹性纤维组装中具有重要的非补偿作用。我们已经确定了它们如何与原弹性蛋白，赖氨酰氧化酶和β-内酰胺酶-1相互作用，从而揭示了它们如何差异调节组装。纤蛋白-4和赖氨酰氧化酶之间的强结合增强了纤蛋白-4与原弹性蛋白的相互作用，形成可指导弹性蛋白交联的三元复合物。相比之下，fibulin-5没有强烈结合赖氨酰氧化酶，但在末端和中心区域结合原弹性蛋白，并可以同时结合fibulin-4。这两种纤蛋白差异结合N-末端的reflectin-1，强烈抑制其结合赖氨酰氧化酶和原弹性蛋白。敲除实验表明，fibulin-5控制微纤维上的弹性蛋白沉积，尽管fibulin-4也可以结合纤维蛋白-1。这些实验提供了纤蛋白-4和-5在弹性纤维组装中的不同作用以及它们如何协同作用以将分子伴侣交联的弹性蛋白陪伴到微纤维上的分子帐户。
Fibulin-4 and -5 are extracellular glycoproteins with essential non-compensatory roles in elastic fiber assembly. We have determined how they interact with tropoelastin, lysyl oxidase, and fibrillin-1, thereby revealing how they differentially regulate assembly. Strong binding between fibulin-4 and lysyl oxidase enhanced the interaction of fibulin-4 with tropoelastin, forming ternary complexes that may direct elastin cross-linking. In contrast, fibulin-5 did not bind lysyl oxidase strongly but bound tropoelastin in terminal and central regions and could concurrently bind fibulin-4. Both fibulins differentially bound N-terminal fibrillin-1, which strongly inhibited their binding to lysyl oxidase and tropoelastin. Knockdown experiments revealed that fibulin-5 controlled elastin deposition on microfibrils, although fibulin-4 can also bind fibrillin-1. These experiments provide a molecular account of the distinct roles of fibulin-4 and -5 in elastic fiber assembly and how they act in concert to chaperone cross-linked elastin onto microfibrils.