Functions of VAMP proteins in glial cells

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。我们关注神经元突触连接周围的神经胶质细胞，我们的目标是验证一个长期存在的假设，即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，我们结合了我们在过去几年中开发的新的和独特的实验方法，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的方法。我们的项目跟进并扩展了合作伙伴之前的合作，该合作导致了最近的第一次出版。具体而言，我们将研究神经胶质细胞中几种所谓的囊泡相关膜蛋白（VAMPs）的消除如何影响神经胶质细胞的生理特性以及选定脑区域的组织学和超微结构。VAMP家族的成员是高度保守且普遍表达的蛋白质复合物组分，其催化膜的靶向融合，从而介导细胞器之间的囊泡胞内运输。这是真核细胞的一个关键过程。我们注意到，以往的研究几乎只关注VAMPs在神经元中的功能，而它们在神经胶质细胞中的作用长期被忽视。我们希望，这个为期两年的探索性项目的结果将使我们能够在未来扩大建议和对拨款的需求。我们的项目完全依赖于法国和德国合作伙伴之间的双边合作，他们在神经元-胶质细胞相互作用方面有着共同和长期的兴趣和记录，并且他们拥有高度互补的方法，这将使项目能够有效地执行。这个项目属于基础研究的范畴，但我们的结果可能会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发展，并加强我们两国在国际上极具竞争力的研究领域的地位。

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.