Pannexin signalling in neural progenitor cells

神经元是大脑中负责信息传输的细胞。神经发生，即制造新神经元的过程，发生在特定的大脑区域，甚至在出生后，对某些关键的大脑功能，如记忆，是重要的。由于神经前体细胞的存在，大脑中对记忆至关重要的部分--海马体中的神经发生成为可能。这些特化细胞与干细胞有一些共同的特性，这意味着它们可以分裂形成新的祖细胞，和/或分化为神经元或其他类型的细胞，称为神经胶质细胞。这些干细胞样祖细胞的命运高度受控于局部环境因素，如电活动、生长因子和其他小分子。我们才刚刚开始了解维持这一重要的祖细胞池并调节它们向神经元分化的复杂成分。在细胞膜中形成水通道的蛋白质正在成为重要的媒介，负责向这些细胞传递环境线索。Pannexins是哺乳动物中形成大孔通道的一组蛋白质，这些通道允许离子和小分子通过。我们的工作发现，在海马神经祖细胞中存在两种类型的膜联蛋白，即膜联蛋白1和膜联蛋白2，并可能在它们的调控中发挥关键作用。我们的建议旨在通过增加我们对神经前体细胞通道功能的了解，并通过确定它们参与的细胞过程来揭示pAnnexin 1和pannin 2是如何影响神经前体细胞的。我们的研究结果将有助于了解在大脑中创造新神经元的能力背后的因素，以及这一非凡的基本过程是如何在一生中保持的。

Neurons are the cells in the brain responsible for information transmission. Neurogenesis, the process of the making new neurons, occurs in specific brain regions, even after birth, and is important for certain critical brain functions, such as memory. Neurogenesis in the hippocampus, the part of the brain important for memory, is made possible by the presence of neural progenitor cells. These specialized cells share some properties with stem cells, meaning they can divide to form new progenitor cells, and/or differentiate into either neurons or other types of cells called glia. The fate of these stem-like progenitor cells is highly controlled by local environmental factors such as electrical activity, growth factors and other small molecules. We are only beginning to understand the complex components that maintain this important pool of progenitor cells and regulate their differentiation into neurons. Proteins that form aqueous channels in membranes are emerging as important mediators responsible for transmitting environmental cues to these cells. Pannexins are a family of proteins in mammals forming large-pore channels that allow the passage of ions and small molecules. Our work has found that two types of pannexins, pannexin 1 and pannexin 2, are present in hippocampal neural progenitor cells and may play key roles in their regulation. Our proposal aims to uncover how pannexin 1 and pannexin 2 affect neural progenitor cells by increasing our understanding of their channel functions and through identifying the cellular processes in which they participate. The results of our studies will contribute to the knowledge of the factors underlying the ability to create new neurons in the brain, and how this remarkable fundamental process is maintained throughout life.