Rab GTPases and Neuroendocytosis

Rab GTP 酶和神经内吞作用

• 批准号: 9974517
• 负责人: Lisa Elferink
• 金额: $ 34.45万
• 依托单位: Wayne State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2001-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9974517&HistoricalAwards=false
• 关键词: Rab; GTPases; Neuroendocytosis

Proposal #9974517Lisa ElferinkSynaptic transmission is the primary form of communication between neurons. It is a highly regulated process that underlies virtually all neuronalpathways, from simple reflexes to higher order brain function such as learning and memory. Synaptic transmission involves the release of neurotransmitters from synaptic and secretory vesicles by exocytosis followed by the retrieval of vesicle membranes by endocytosis. Therefore endocytosis is essential for the continued secretory function of neural cells. Impairment of this process is likely to result in paralysis or mental disorders. The long term goal of this proposal is to examine the molecular mechanism mediating secretory vesicle recycling and its role in synaptic transmission. Rab GTPases are a family of monomeric proteins involved in membrane transport. Rab15 will form a focal point for these studies since its expression is enriched over other endosomal rabs in cells with high levels of secretion such as neurons and neuroendocrine cells. Moreover, rab15 localizes to early endosomes in non-neuronal cells, consistent with its proposed role in endocytosis. This proposal describes experiments that examine the role of rab15 in secretory vesicle recycling. First we will identify the endocytic transport step regulated by rab15 in non-neuronal cells - key findings will be applied to neuroendocrine cells.Second, we will determine rab15's subcellular localization in neuroendocrine cells. Finally, we will examine the role of rab15 in secretory vesicle recycling. Together, these studies will shed new lighton the role of rab15 in regulating the recycling of secretory vesicles during synaptic transmission and more generally, on the molecular mechanisms determining the specificity of endocytosis in all cell types.

提案＃9974517LISA ElferinkSynaptic传播是神经元之间通信的主要形式。 这是一个高度调节的过程，它几乎是所有神经元路径的基础，从简单的反射到高级大脑功能，例如学习和记忆。 突触传播涉及通过胞吐作用从突触和分泌囊泡中释放出神经递质，然后通过内吞作用检索囊泡膜。 因此，内吞作用对于神经细胞的持续分泌功能至关重要。 这一过程的损害可能导致瘫痪或精神障碍。 该提案的长期目标是检查介导分泌囊泡回收及其在突触传播中的作用的分子机制。 RAB GTPases是参与膜运输的单体蛋白质家族。 RAB15将成为这些研究的焦点，因为它的表达富集于具有高水平分泌的细胞（例如神经元和神经内分泌细胞）的细胞中。 此外，RAB15定位于非神经元细胞的早期内体，与其在内吞作用中的作用一致。 该建议描述了研究RAB15在分泌囊泡回收中的作用的实验。 首先，我们将确定由RAB15在非神经元细胞中调节的内吞传输步骤 - 关键发现将应用于神经内分泌细胞。第二，我们将确定RAB15在神经内分泌细胞中的亚细胞定位。 最后，我们将研究Rab15在分泌囊泡回收中的作用。 总之，这些研究将使新的莱顿在突触传播过程中调节分泌囊泡的回收以及在确定所有细胞类型内内吞作用的特异性的分子机制上的作用。