Structural Insights into Reelin Function: Present and Future.
Structural Insights into Reelin Function: Present and Future.
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DOI：
10.3389/fncel.2016.00137
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发表时间：
2016
影响因子：
5.3
通讯作者：
Comoletti D
中科院分区：
文献类型：
--
作者：
Ranaivoson FM;von Daake S;Comoletti D
Reelin是由大脑皮层和海马的边缘区域中的Cajal-Retzius细胞分泌的神经元糖蛋白，在大脑发育期间，Reelin在控制神经元迁移和细胞层形成中起重要作用。这种3461个残基长的蛋白质由信号肽、F-spondin样结构域、8个Reelin重复序列（RR 1 -8）和C-末端的带正电荷的序列组成。生化数据表明，Reelin的中心区域与低密度脂蛋白受体载脂蛋白E受体2（ApoER 2）和极低密度脂蛋白受体（VLDLR）结合，导致细胞内衔接蛋白Dab 1磷酸化。分泌后，Reelin迅速降解为三个主要片段，但这种降解的功能意义知之甚少。可能是由于其巨大的质量和其结构的复杂性，Reelin的高分辨率，三维结构从未被确定。然而，一些RR的晶体结构已经得到解决，为它们的折叠和与ApoER 2受体的相互作用提供了重要的见解。这篇综述讨论了目前的研究结果的结构上的Reelin和它的结合ApoER 2和VLDLR受体，我们讨论了一些领域，蛋白质组学和结构生物学可以帮助了解Reelin在大脑发育和人类健康的功能。
Reelin is a neuronal glycoprotein secreted by the Cajal-Retzius cells in marginal regions of the cerebral cortex and the hippocampus where it plays important roles in the control of neuronal migration and the formation of cellular layers during brain development. This 3461 residue-long protein is composed of a signal peptide, an F-spondin-like domain, eight Reelin repeats (RR1–8), and a positively charged sequence at the C-terminus. Biochemical data indicate that the central region of Reelin binds to the low-density lipoprotein receptors apolipoprotein E receptor 2 (ApoER2) and the very-low-density lipoprotein receptor (VLDLR), leading to the phosphorylation of the intracellular adaptor protein Dab1. After secretion, Reelin is rapidly degraded in three major fragments, but the functional significance of this degradation is poorly understood. Probably due to its large mass and the complexity of its architecture, the high-resolution, three-dimensional structure of Reelin has never been determined. However, the crystal structures of some of the RRs have been solved, providing important insights into their fold and the interaction with the ApoER2 receptor. This review discusses the current findings on the structure of Reelin and its binding to the ApoER2 and VLDLR receptors, and we discuss some areas where proteomics and structural biology can help understanding Reelin function in brain development and human health.