Reelin is a secreted glycoprotein recognized by the CR-50 monoclonal antibody
Reelin is a secreted glycoprotein recognized by the CR-50 monoclonal antibody
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DOI：
10.1523/jneurosci.17-01-00023.1997
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发表时间：
1997-01-01
影响因子：
5.3
通讯作者：
Curran, T
中科院分区：
文献类型：
--
作者：
DArcangelo, G;Nakajima, K;Curran, T
神经学上的小鼠突变品系reeler由于神经发育过程中细胞迁移缺陷，其多个脑结构呈现出异常的层状组织。这种表型是reelin基因被破坏的结果，reelin基因编码一种具有细胞外基质蛋白若干结构特征的蛋白质。为了理解Reelin对神经元迁移作用的分子基础，我们构建了一个全长的reelin克隆，并利用它来指导Reelin的表达。在此，我们证明Reelin是一种分泌型糖蛋白，并且一个高度带电的C末端区域对分泌至关重要。此外，我们证明Reelin的N末端区域存在的一个氨基酸序列包含一个能被CR - 50单克隆抗体识别的表位。CR - 50是针对正常小鼠大脑中表达而在reeler小鼠中缺失的一种抗原产生的。CR - 50与其表位的相互作用导致体外神经细胞聚集的破坏。在此，我们利用CR - 50从用reelin mRNA编程的网织红细胞提取物、用reelin克隆转染的细胞以及小脑外植体中沉淀Reelin。reelin基因产物似乎在神经元迁移的调节中作为一种指导性信号发挥作用。
The neurological mouse mutant strain reeler displays abnormal laminar organization of several brain structures as a consequence of a defect in cell migration during neurodevelopment. This phenotype is a result of the disruption of reelin, a gene encoding a protein that has several structural characteristics of extracellular matrix proteins. To understand the molecular basis of the action of Reelin on neuronal migration, we constructed a full-length reelin clone and used it to direct Reelin expression. Here, we demonstrate that Reelin is a secreted glycoprotein and that a highly charged C-terminal region is essential for secretion. In addition, we demonstrate that an amino acid sequence present in the N-terminal region of Reelin contains an epitope that is recognized by the CR-50 monoclonal antibody. CR-50 was raised against an antigen expressed in normal mouse brain that is absent in reeler mice. The interaction of CR-50 with its epitope leads to the disruption of neural cell aggregation in vitro. Here, we used CR-50 to precipitate Reelin from reticulocyte extracts programmed with reelin mRNA, from cells transfected with reelin clones, and from cerebellar explants. The reelin gene product seems to function as an instructive signal in the regulation of neuronal migration.