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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Lack of the endosomal SNAREs vti1a and vti1b led to significant impairments in neuronal development
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Lack of the endosomal SNAREs vti1a and vti1b led to significant impairments in neuronal development

机译:内体SNAREs vti1a和vti1b的缺乏导致神经元发育的重大损害

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摘要

Fusion between membranes is mediated by specific SNARE complexes. Here we report that f ibroblasts survive the absence of the trans-Golgi network/early endosomal SNARE vtila and the late endosomal SNARE vti1b with intact organelle morphology and minor trafficking defects. Because vtila and vti1b are the only members of their SNARE subclass and the yeast homolog Vti1p is essential for cell survival, these data suggest that more distantly related SNAREs acquired the ability to function in endosomal traffic during evolution. However, absence of vtila and vti1b resulted in perinatal lethality. Major axon tracts were missing, reduced in size, or misrouted in Vti1a~(-/-) Vti1b~(-/-) embryos. Progressive neurode-generation was observed in most Vti1a~(-/-) Vti1b~(-/-) peripheral ganglia. Neurons were reduced by more than 95% in Vti1a~(-/-) Vti1b~(-/-)dorsal root and geniculate ganglia at embryonic day 18.5. These data suggest that special demands for endosomal membrane traffic could not be met in Vti1a~(-/-) Vti1b~(-/-) neurons. Vti1a~(-/-) and Vti1b~(-/-)single deficient mice were viable without these neuronal defects, indicating that they can substitute for each other in these processes.
机译:膜之间的融合是由特定的SNARE复合物介导的。在这里,我们报道成纤维细胞在没有完整的细胞器形态和较小的运输缺陷的情况下幸免于反高尔基网络/早期内体SNARE vtila和晚期内体SNARE vti1b。由于vtila和vti1b是其SNARE亚类的唯一成员,并且酵母同源物Vti1p对于细胞存活至关重要,因此这些数据表明,更远相关的SNARE在进化过程中获得了在内体运输中发挥功能的能力。但是,缺乏vtila和vti1b会导致围产期致死。 Vti1a〜(-/-)Vti1b〜(-/-)胚胎中的主要轴突束缺失,尺寸减小或路线错误。在大多数Vti1a〜(-/-)Vti1b〜(-/-)周围神经节中观察到进行性神经变性。胚胎第18.5天,Vti1a〜(-/-)Vti1b〜(-/-)背根和膝状神经节神经元减少了95%以上。这些数据表明,在Vti1a〜(-/-)Vti1b〜(-/-)神经元中无法满足对内体膜运输的特殊需求。 Vti1a〜(-/-)和Vti1b〜(-/-)单缺陷小鼠在没有这些神经元缺陷的情况下是可行的,这表明它们可以在这些过程中相互替代。

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  • 作者单位

    Department of Neuroanatomy, Center of Anatomy, University of Goettingen, 37075 Goettingen, Germarly;

    Department of Neuroanatomy, Center of Anatomy, University of Goettingen, 37075 Goettingen, Germarly;

    Department of Biochemistry III, Bielefeld University, 33615 Bielefeld, Germany;

    Department of Biochemistry III, Bielefeld University, 33615 Bielefeld, Germany;

    Department of Neuroanatomy, Center of Anatomy, University of Goettingen, 37075 Goettingen, Germarly;

    Department of Biochemistry III, Bielefeld University, 33615 Bielefeld, Germany;

    Department of Neuroanatomy, Center of Anatomy, University of Goettingen, 37075 Goettingen, Germarly;

    Department of Neuroanatomy, Center of Anatomy, University of Goettingen, 37075 Goettingen, Germarly,Freiburg Institute for Advanced Studies, School of Life Sciences (FRIAS) and Department of Molecular Embryology,University of Freiburg, 79104 Freiburg, Germany;

    Department of Biochemistry III, Bielefeld University, 33615 Bielefeld, Germany;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    endosome; neurite outgrowth; neuronal survival;

    机译:内体;神经突长出;神经元存活;

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