Collapsin response mediator proteins of neonatal rat brain interact with chondroitin sulfate
Collapsin response mediator proteins of neonatal rat brain interact with chondroitin sulfate
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DOI：
10.1074/jbc.m210181200
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发表时间：
2003-01-31
影响因子：
4.8
通讯作者：
Kappler, J
中科院分区：
文献类型：
--
作者：
Franken, S;Junghans, U;Kappler, J
硫酸软骨素蛋白聚糖是中枢神经系统细胞外基质的结构和功能的重要组成部分。它们在发育中的哺乳动物脑中的表达受到精确调节，细胞培养实验表明这些蛋白聚糖参与细胞粘附、神经元迁移、神经突形成、神经元极化和神经元存活的控制。在这里，我们报告说，从新生大鼠大脑的硫酸软骨素结合蛋白的单克隆抗体，识别神经肽反应介导蛋白-4（CRMP-4），这属于一个家庭的蛋白质参与神经肽/信号蛋白3A信号。新生大鼠脑中可溶性CRMPs与硫酸软骨素亲和柱结合，CRMPs特异性抗血清共沉淀硫酸软骨素。此外，硫酸软骨素和CRMP-4被发现定位于重叠分布在边缘区和基板的大脑皮质的化学。细胞死亡后，CRMP被释放到NTera-2前体细胞和新皮层神经元的培养上清液中，CRMP-4在新生大鼠的上皮层板中强烈表达，其中细胞死亡丰富。因此，自然发生的细胞死亡是一种合理的机制，在某些发育阶段将CRMP靶向细胞外基质。总之，我们的数据表明，CRMPs，除了其作为胞质信号转导分子的作用，可能subserve作为细胞外基质的配体在发育中的大脑中的未知功能。
Chondroitin sulfate proteoglycans are structurally and functionally important components of the extracellular matrix of the central nervous system. Their expression in the developing mammalian brain is precisely regulated, and cell culture experiments implicate these proteoglycans in the control of cell adhesion, neuron migration, neurite formation, neuronal polarization, and neuron survival. Here, we report that a monoclonal antibody against chondroitin sulfate-binding proteins from neonatal rat brain recognizes collapsin response mediator protein-4 (CRMP-4), which belongs to a family of proteins involved in collapsin/semaphorin 3A signaling. Soluble CRMPs from neonatal rat brain bound to chondroitin sulfate affinity columns, and CRMP-specific antisera co-precipitated chondroitin sulfate. Moreover, chondroitin sulfate and CRMP-4 were found to be localized immunohistochemically in overlapping distributions in the marginal zone and the subplate of the cerebral cortex. CRMPs are released to culture supernatants of NTera-2 precursor cells and of neocortical neurons after cell death, and CRMP-4 is strongly expressed in the upper cortical plate of neonatal rat where cell death is abundant. Therefore, naturally occurring cell death is a plausible mechanism that targets CRMPs to the extracellular matrix at certain stages of development. In summary, our data indicate that CRMPs, in addition to their role as cytosolic signal transduction molecules, may subserve as yet unknown functions in the developing brain as ligands of the extracellular matrix.