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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >RAB-5 and RAB-10 cooperate to regulate neuropeptide release in Caenorhabditis elegans
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RAB-5 and RAB-10 cooperate to regulate neuropeptide release in Caenorhabditis elegans

机译:RAB-5和RAB-10协同调节秀丽隐杆线虫中神经肽的释放

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摘要

Neurons secrete neuropeptides from dense core vesicles (DCVs) to modulate neuronal activity. Little is known about how neurons manage to differentially regulate the release of synaptic vesicles (SVs) and DCVs. To analyze this, we screened all Caenorhabditis elegans Rab GTPases and Tre2/Bub2/Cdc16 (TBC) domain containing GTPase-activating proteins (GAPs) for defects in DCV release from C elegans motoneurons. rab-5 and rab-10 mutants show severe defects in DCV secretion, whereas SV exocytosis is unaffected. We identified TBC-2 and TBC-4 as putative GAPs for RAB-5 and RAB-10, respectively. Multiple Rabs and RabGAPs are typically organized in cascades that confer directionality to membrane-trafficking processes. We show here that the formation of release-competent DCVs requires a reciprocal exclusion cascade coupling RAB-5 and RAB-10, in which each of the two Rabs recruits the other's GAP molecule. This contributes to a separation of RAB-5 and RAB-10 domains at the Golgi-endosomal interface, which is lost when either of the two GAPs is inactivated. Taken together, our data suggest that RAB-5 and RAB-10 cooperate to locally exclude each other at an essential stage during DCV sorting.
机译:神经元从致密核心囊泡(DCV)分泌神经肽来调节神经元活性。关于神经元如何设法差异调节突触小泡(SVs)和DCVs的释放知之甚少。为了对此进行分析,我们筛选了所有秀丽隐杆线虫Rab GTPases和含有GTPase激活蛋白(GAPs)的Tre2 / Bub2 / Cdc16(TBC)域中是否存在线虫秀丽隐杆线虫释放DCV的缺陷。 rab-5和rab-10突变体显示DCV分泌严重缺陷,而SV胞吐作用不受影响。我们将TBC-2和TBC-4分别确定为RAB-5和RAB-10的公认GAP。多个Rabs和RabGAP通常以级联的形式进行组织,从而赋予膜运输过程以方向性。我们在这里显示,具有释放能力的DCV的形成需要相互排斥的级联偶联RAB-5和RAB-10,其中两个Rab各自募集对方的GAP分子。这有助于在高尔基体-内体界面处分离RAB-5和RAB-10结构域,当两个GAP中的任何一个失活时,该结构就会丢失。两者合计,我们的数据表明RAB-5和RAB-10在DCV分选的关键阶段进行合作,将彼此局部排斥。

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  • 作者单位

    Department of Molecular Neurogenetics, European Neuroscience Institute, 37077 Goettingen, Germany,Stimulated Emission Depletion (STED) Microscopy of Synaptic Function, Department of Neuro- and Sensory Physiology, University of Goettingen, Gottingen, Germany,International Max Planck Research School Neurosciences, 37077 Goettingen, Germany;

    Department of Molecular Neurogenetics, European Neuroscience Institute, 37077 Goettingen, Germany,International Max Planck Research School Neurosciences, 37077 Goettingen, Germany;

    Department of Molecular Neurogenetics, European Neuroscience Institute, 37077 Goettingen, Germany,International Max Planck Research School Molecular Biology, 37077 Goettingen, Germany;

    Department of Molecular Neurogenetics, European Neuroscience Institute, 37077 Goettingen, Germany,Department of Molecular Neurogenetics, Center for Molecular Physiology of the Brain, 37077 Goettingen, Germany;

    Institute of Biochemistry, Johann Wolfgang Goethe University Frankfurt, 60438 Frankfurt, Germany;

    Department of Molecular Neurogenetics, European Neuroscience Institute, 37077 Goettingen, Germany;

    Department of Molecular Neurogenetics, European Neuroscience Institute, 37077 Goettingen, Germany,Department of Molecular Neurogenetics, Center for Molecular Physiology of the Brain, 37077 Goettingen, Germany;

    Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854;

    Stimulated Emission Depletion (STED) Microscopy of Synaptic Function, Department of Neuro- and Sensory Physiology, University of Goettingen, Gottingen, Germany,Department of Molecular Neurogenetics, Center for Molecular Physiology of the Brain, 37077 Goettingen, Germany;

    Institute of Biochemistry, Johann Wolfgang Goethe University Frankfurt, 60438 Frankfurt, Germany;

    Department of Molecular Neurogenetics, European Neuroscience Institute, 37077 Goettingen, Germany,Department of Molecular Neurogenetics, Center for Molecular Physiology of the Brain, 37077 Goettingen, Germany,Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854;

  • 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

    neurosecretion; trans-Golgi; network; sorting;

    机译:神经分泌反高尔基网络;分类;

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