Novel regulators of neural endosomes

神经内体的新型调节剂

• 批准号: RGPIN-2016-04579
• 负责人: Swayne, LeighAnne
• 金额: $ 2.4万
• 依托单位: University of Victoria
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=615156
• 关键词: Novel; regulators; neural; endosomes

The proper development of the brain is a complex and finely-tuned process. There are widespread implications for learning and memory as well as the development of all sensory and motor functions. The cells in the brain that transmit information (neurons) undergo tremendous structural changes as they develop in order to set up connections within the brain and between the brain and the rest of the body. At the molecular level, an important protein family that my lab has recently identified as being involved in this process are the “pannexins”. The pannexins are known to form channels (like gated doors) in cell membranes that help allow passage of ions and metabolites that act as signals between cells. While the study of pannexins has previously focused on their role on the membranes at the surface of cells, we and others recently found that the pannexins are also found on the membranes of a specialized compartment inside the cell. This “endosome” compartment plays a key role in neurons during development by acting as a source of membrane required to build the new processes connecting neurons together (neurites). This compartment also regulates the functions of many of the other proteins (such as receptors) involved in directing the creation of neurites. The goal of this research program is to shed light on molecular factors governing the trafficking of pannexins to endosomes. Further, this will allow us to capitalize on this newly generated knowledge to determine the role of pannexins in regulating the basic properties and functions of endosomes in developing and mature neurons. Results from this work will make important contributions to new areas of knowledge development with respect to the distribution and roles of pannexins in neural cells, the regulation of the endosome compartment by ion and metabolite channels and the factors regulating the growth of neurites. These results will improve our understanding of the molecular mechanisms underlying critical brain activities like memory and learning.

大脑的正常发育是一个复杂而精细的过程。这对学习和记忆以及所有感觉和运动功能的发展都有广泛的影响。大脑中传递信息的细胞（神经元）在发育过程中经历了巨大的结构变化，以便在大脑内部以及大脑与身体其他部分之间建立联系。在分子水平上，我的实验室最近发现了一个重要的蛋白质家族，即“泛内联蛋白”，参与了这一过程。众所周知，泛联蛋白在细胞膜上形成通道（就像门一样），帮助离子和代谢物在细胞之间传递信号。虽然以前对泛联蛋白的研究主要集中在它们在细胞表面的膜上的作用，但我们和其他人最近发现，泛联蛋白也存在于细胞内一个专门的隔室的膜上。这种“核内体”隔室在神经元发育过程中起着关键作用，作为建立连接神经元的新过程（神经突）所需的膜的来源。这个隔室还调节许多其他蛋白质（如受体）的功能，这些蛋白质参与指导神经突的形成。本研究计划的目标是阐明控制泛内联蛋白到核内体的运输的分子因素。此外，这将使我们能够利用这一新产生的知识来确定泛连接蛋白在调节发育和成熟神经元内体的基本特性和功能中的作用。这项工作的结果将对泛肽在神经细胞中的分布和作用、离子和代谢物通道对核内体室的调节以及调节神经突生长的因素的新知识领域的发展做出重要贡献。这些结果将提高我们对记忆和学习等关键大脑活动的分子机制的理解。