Ambrosio Andrea L, Taelman Vincent F, Lee Hojoon X, Metzinger Carrie A, Coffinier Catherine, De Robertis E M
Howard Hughes Medical Institute, Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Dev Cell. 2008 Aug;15(2):248-60. doi: 10.1016/j.devcel.2008.06.013.
Vertebrate Crossveinless-2 (CV2) is a secreted protein that can potentiate or antagonize BMP signaling. Through embryological and biochemical experiments we find that: (1) CV2 functions as a BMP4 feedback inhibitor in ventral regions of the Xenopus embryo; (2) CV2 complexes with Twisted gastrulation and BMP4; (3) CV2 is not a substrate for tolloid proteinases; (4) CV2 binds to purified Chordin protein with high affinity (K(D) in the 1 nM range); (5) CV2 binds even more strongly to Chordin proteolytic fragments resulting from Tolloid digestion or to full-length Chordin/BMP complexes; (6) CV2 depletion causes the Xenopus embryo to become hypersensitive to the anti-BMP effects of Chordin overexpression or tolloid inhibition. We propose that the CV2/Chordin interaction may help coordinate BMP diffusion to the ventral side of the embryo, ensuring that BMPs liberated from Chordin inhibition by tolloid proteolysis cause peak signaling levels.
脊椎动物的无交叉静脉-2（CV2）是一种分泌蛋白，可增强或拮抗骨形态发生蛋白（BMP）信号传导。通过胚胎学和生化实验，我们发现：（1）CV2在非洲爪蟾胚胎的腹侧区域作为BMP4反馈抑制剂发挥作用；（2）CV2与扭曲原肠胚形成蛋白和BMP4形成复合物；（3）CV2不是类 tolloid 蛋白酶的底物；（4）CV2与纯化的脊索蛋白具有高亲和力结合（解离常数K(D)在1 nM范围内）；（5）CV2与经类 tolloid 消化产生的脊索蛋白水解片段或全长脊索蛋白/BMP复合物结合得更强；（6）CV2的缺失会导致非洲爪蟾胚胎对脊索蛋白过表达或类 tolloid 抑制的抗BMP效应变得高度敏感。我们认为，CV2/脊索蛋白的相互作用可能有助于协调BMP向胚胎腹侧的扩散，确保经类 tolloid 蛋白水解作用从脊索蛋白抑制中释放出来的BMP引起峰值信号水平。
