The role of dense core vesicles in synapse formation

致密核心囊泡在突触形成中的作用

• 批准号: 6893692
• 负责人: Clarissa Leigh Waites
• 金额: $ 5.15万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-15 至 2006-04-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6893692
• 关键词: antisense nucleic acid; chimeric proteins; complementary DNA; developmental neurobiology; hippocampus; immunocytochemistry; immunoelectron microscopy; laboratory rat; neural plasticity; neurons; optics; polymerase chain reaction; postdoctoral investigator; protein localization; protein protein interaction; protein transport; secretory protein; synaptic vesicles; synaptogenesis; transfection /expression vector

DESCRIPTION (provided by applicant): A central question in neuroscience is how individual neurons connect with one another during development. However, mechanisms of synapse formation are still poorly understood. Many of the proteins and organelles present at mature synapses have been identified, but how these components arrive at newly forming synapses is not known. Two recent studies, including one from this laboratory, have implicated dense core vesicles (DCVs) in the transport of proteins to the presynaptic active zone during synapse formation. DCVs are a major type of secretory vesicle involved in signaling between neurons. They secrete neuropeptides, hormones, neurotrophins and certain neurotransmitters. These studies now suggest an additional role for DCVs in the transport of presynaptic proteins to newly forming synapses. The goals of this proposal are to determine whether the DCVs involved in protein transport differ from those involved in secretion, and to understand the precise role of DCVs in synapse formation. In the first two specific aims, we will use immunostaining and optical imaging to describe the properties of DCVs involved in protein transport. In the third specific aim, we will use antisense RNAs to reduce or eliminate DCVs in developing neurons, then examine how synapse formation is affected.

描述（由申请人提供）：神经科学的一个中心问题是个体神经元在发育过程中如何相互连接。然而，突触形成的机制仍然知之甚少。许多存在于成熟突触中的蛋白质和细胞器已经被鉴定出来，但这些成分如何到达新形成的突触尚不清楚。最近的两项研究，包括本实验室的一项研究，表明在突触形成过程中，致密核心囊泡（DCV）参与了蛋白质向突触前活动区的转运。DCV是参与神经元之间信号传导的主要类型的分泌囊泡。它们分泌神经肽、激素、神经营养素和某些神经递质。这些研究表明，DCV在突触前蛋白向新形成的突触的转运中起着额外的作用。该提案的目标是确定参与蛋白质转运的DCV是否与参与分泌的DCV不同，并了解DCV在突触形成中的确切作用。在前两个具体目标中，我们将使用免疫染色和光学成像来描述参与蛋白质转运的DCV的特性。在第三个具体目标中，我们将使用反义RNA减少或消除发育中神经元中的DCV，然后研究突触形成如何受到影响。