Molecular Mechanism of corticohistoqenesis of the brain

Reelin是大脑中有序神经元排列的关键介质。在这里，我们证明了Reelin分子在体外和体内相互组装形成一个巨大的蛋白质复合物。功能阻断抗Reelin抗体CR-50明显抑制Reelin-Reelin相互作用，其浓度已知可抑制Reelin功能。这种组装是通过CR-50表位区α-螺旋结构域的静电相互作用介导的。重组CR-50表位片段自发形成可溶的、具有规则重复结构的弦状均聚物，由40多个单体组成。这些数据表明，Reelin通过组成一个由CR-50表位区驱动的大蛋白组装来发挥其生物学功能，提出了一种新的Reelin信号通路在神经发育中的模型。

Reelin is a key mediator of ordered neuronal alignment in the brain. Here we demonstrate that Reelin molecules assemble each other to forms a huge protein complex both in vitro and in vivo. The Reelin-Reelin interaction is clearly inhibited by the function-blocking anti-Reelin antibody, CR-50, at a concentration known to inhibit Reelin function. This assembly is mediated by electrostatic interaction via the α-helix domains in the CR-50 epitope region. Recombinant CR-50 epitope fragments spontaneously constitute a soluble, string-like homopolymer with a regularly repeated structure composed of more than 40 monomers. These data suggest that Reelin exerts its biological function by composing a large protein assembly driven by the CR-50 epitope region, proposing a novel model of the Reelin signaling in neurodevelopment.