Functions of VAMP proteins in glial cells

神经胶质细胞中VAMP蛋白的功能

• 批准号: 242852401
• 负责人: Professorin Dr. Antje Grosche
• 金额: --
• 依托单位: Institut des Neurosciences Cellulaires et Intégratives (INCI)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/242852401?language=en
• 关键词: Functions; VAMP; proteins; glial; cells

Our project addresses a key question in neuroscience, namely how cells of the central nervous system interact to assure its proper development and function. We focus on glial cells that surround synaptic connections between neurons, and we aim to test a long-standing hypothesis that these cells influence the development and function of neurons by the vesicular transport and release of substances. To test this hypothesis, we combine new and unique experimental approaches that we have developed within the last years including new transgenic mouse models and methods to assess the morphology and physiology of glial cells. Our project follows up and extends a previous collaboration of the partners that has led to a first recent publication. Concretely, we will investigate how elimination of several so-called vesicle-associated membrane proteins (VAMPs) in glial cells affects the physiologic properties of glial cells and the histology and ultrastructure of selected brain regions. Members of the VAMP family are highly conserved and ubiquitously expressed components of protein complexes that catalyse the targeted fusion of membranes and thereby mediate the intracellular transport of vesicles between organelles. This is a key process of eukaryotic cells. We note that previous research has focused almost exclusively on the functions of VAMPs in neurons, and their role in glial cells has been neglected for a long time. We hope that the results of our exploratory two-year project will enable an expansion of the proposal and the demand of grants in the future. Our project relies entirely on a bilateral cooperation between a French and a German partner, who both have a common and long-standing interest and track record in neuron-glia interactions and who command highly complementary methods that will enable an efficient execution of the project. This project falls in the category of fundamental research, but our results may have implications for R&D in the pharmaceutical and biotechnological industry, if they uncover glial signaling pathways as potential therapeutic targets for brain diseases. Last not least, we hope that our transnational project will advance neuroscience in France and Germany and strengthen the position of our countries in a field of research that is highly competitive at an international level.

我们的项目解决了神经科学中的一个关键问题，即中枢神经系统的细胞如何相互作用以确保其正常发育和功能。我们专注于神经元之间的突触连接周围的神经胶质细胞，我们的目标是测试一个长期存在的假设，这些细胞通过囊泡运输和物质释放影响神经元的发育和功能。为了验证这一假设，我们联合收割机结合了过去几年开发的新的独特实验方法，包括新的转基因小鼠模型和评估神经胶质细胞形态和生理学的方法。我们的项目跟进并扩展了合作伙伴之前的合作，这导致了最近的第一次出版。具体地说，我们将研究如何消除几个所谓的囊泡相关膜蛋白（VAMP）在神经胶质细胞影响神经胶质细胞的生理特性和选定的大脑区域的组织学和超微结构。VAMP家族的成员是蛋白复合物的高度保守和普遍表达的组分，其催化膜的靶向融合，从而介导囊泡在细胞器之间的细胞内转运。这是真核细胞的一个关键过程。我们注意到，以前的研究几乎只集中在神经元中VAMP的功能，而它们在胶质细胞中的作用长期被忽视。我们希望，我们为期两年的探索性项目的结果将使我们能够在未来扩大该提案和赠款需求。我们的项目完全依赖于一个法国和一个德国合作伙伴之间的双边合作，他们在神经胶质相互作用方面都有着共同和长期的兴趣和记录，他们掌握着高度互补的方法，这将使项目的有效执行成为可能。该项目福尔斯基础研究的范畴，但我们的研究结果可能对制药和生物技术行业的研发产生影响，如果他们发现神经胶质信号通路是脑部疾病的潜在治疗靶点。最后，我们希望我们的跨国项目将推动法国和德国的神经科学，并加强我们两国在国际竞争激烈的研究领域的地位。