• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Neuropathology: official journal of the Japanese Society of Neuropathology >A unique role of dynein and nud family proteins in corticogenesis
【24h】

A unique role of dynein and nud family proteins in corticogenesis

机译：动力蛋白和裸体家族蛋白在皮质发生中的独特作用

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Heterozygous LIS1 mutations are the most common cause of human lissencephaly, a human neuronal migration defect, and DCX mutations are the most common cause of X-linked lissencephaly. Lissencephaly is characterized by a smooth cerebral surface, thick cortex and dilated lateral ventricles associated with mental retardation and seizures due to defective neuronal migration. Lissencephaly due to the heterozygous loss of the gene LIS1 is a good example of a haploinsufficiency disorder. LIS1 was deleted or mutated in a large proportion of patients with lissencephaly in a heterozygous fashion. A series of studies discovered that LIS1 is an essential regulator of cytoplasmic dynein. Notably, the role of LIS1 in regulating dynein activity is highly conserved among eukaryotes. In particular, we reported that LIS1 and NDEL1 are essential for dynein transport to the plus-end of microtubules by kinesin, which is essential to maintain the proper distribution of cytoplasmic dynein within the cell. In addition, we report that mNUDC (mammalian NUDC) interacts with kinesin-1 and is required for the anterograde transport of a cytoplasmic dynein complex by kinesin-1. A microtubule organization and motor proteins are further modulated by post-translational modifications, including phosphorylation and palmitoylation. These modifications share a common pathway with mitotic cell division. For example, Aurora-A is activated during neurite elongation, and phosphorylates NDEL1, which facilitates microtubule extension into neurite processes. Elucidations of molecular pathways involving neuronal migrations provide us a chance to design a novel strategy for neurological disorder due to defective neuronal migration. For example, inhibition of calpain protects LIS1 from proteolysis resulting in the augmentation of LIS1 levels, which leads to rescue of the phenotypes that are observed in Lis1+/- mice. Endeavoring to address the regulation of the microtubule network and motor proteins will help in understanding not only corticogenesis but neurodegenerative disorders.
机译：杂合的LIS1突变是人类lissencephaly（人类神经元迁移缺陷）的最常见原因，而DCX突变是X连锁lissencephaly的最常见原因。颅脑缺损的特征是大脑表面光滑，皮层厚，侧脑室扩张，与由于神经元迁移不良引起的智力低下和癫痫发作有关。由于LIS1基因杂合性丧失而引起的脑性畸形是单倍体功能不全疾病的一个很好的例子。 LIS1以杂合的方式被删除或突变的大部分脑干患者。一系列研究发现，LIS1是细胞质动力蛋白的必需调节剂。值得注意的是，LIS1在调节动力蛋白活性中的作用在真核生物中高度保守。特别是，我们报道了LIS1和NDEL1对于动力蛋白通过动力蛋白转运至微管的正端是必不可少的，这对于维持细胞内细胞质动力蛋白的正确分布是必不可少的。此外，我们报告mNUDC（哺乳动物NUDC）与kinesin-1相互作用，并且是kinesin-1顺行转运细胞质动力蛋白复合物所必需的。通过翻译后修饰，包括磷酸化和棕榈酰化，进一步调节微管组织和运动蛋白。这些修饰与有丝分裂细胞分裂具有共同的途径。例如，Aurora-A在神经突伸长过程中被激活，并使NDEL​​1磷酸化，这有助于微管向神经突延伸。对涉及神经元迁移的分子途径的阐明为我们提供了一个机会，可以设计由于神经元迁移不良而引起的神经系统疾病的新策略。例如，抑制钙蛋白酶可保护LIS1免受蛋白水解作用，从而导致LIS1水平升高，从而挽救在Lis1 +/-小鼠中观察到的表型。努力解决微管网络和运动蛋白的调节问题将不仅有助于了解皮质发生，而且有助于了解神经退行性疾病。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号