The role of chordin fragments generated by partial tolloid cleavage in regulating BMP activity.
The role of chordin fragments generated by partial tolloid cleavage in regulating BMP activity.
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DOI：
10.1042/bst20150071
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发表时间：
2015-10
影响因子：
3.9
通讯作者：
Baldock C
中科院分区：
文献类型：
--
作者：
Troilo H;Barrett AL;Wohl AP;Jowitt TA;Collins RF;Bayley CP;Zuk AV;Sengle G;Baldock C
软骨介导的骨形态发生蛋白（BMP）家族生长因子的调节在早期胚胎发生和成体体内平衡中是必不可少的。Chordin通过富含半胱氨酸的von Willebrand因子C型（vWC）同源结构域与BMP结合，并阻止它们与其细胞表面受体相互作用。这些结构域也自我关联，并使脊索蛋白靶向相关蛋白质，以微调BMP调节。脊索蛋白-BMP抑制复合物通过分泌的糖蛋白扭曲原肠胚形成（Tsg）加强;然而，抑制通过tolloid家族金属蛋白酶在两个特定位点切割脊索蛋白而减轻。由于Tsg增强了这种切割过程，因此它作为BMP信号传导的促进剂和抑制剂发挥双重作用。最近的发展，在脊索蛋白的研究表明，而不是简单的副产品，切割片段的脊索蛋白继续发挥作用，在BMP的调节。特别地，C-末端的腱蛋白裂解以类型特异性方式增强其抗BMP活性。
Chordin-mediated regulation of bone morphogenetic protein (BMP) family growth factors is essential in early embryogenesis and adult homoeostasis. Chordin binds to BMPs through cysteine-rich von Willebrand factor type C (vWC) homology domains and blocks them from interacting with their cell surface receptors. These domains also self-associate and enable chordin to target related proteins to fine-tune BMP regulation. The chordin–BMP inhibitory complex is strengthened by the secreted glycoprotein twisted gastrulation (Tsg); however, inhibition is relieved by cleavage of chordin at two specific sites by tolloid family metalloproteases. As Tsg enhances this cleavage process, it serves a dual role as both promoter and inhibitor of BMP signalling. Recent developments in chordin research suggest that rather than simply being by-products, the cleavage fragments of chordin continue to play a role in BMP regulation. In particular, chordin cleavage at the C-terminus potentiates its anti-BMP activity in a type-specific manner.