Endosomal pH regulation in neurons: Roles of Na+/H+ exchangers

神经元内体 pH 调节：Na /H 交换器的作用

• 批准号: RGPIN-2015-06790
• 负责人: Numata, Masayuki
• 金额: $ 2.77万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629223
• 关键词: Endosomal; pH; regulation; neurons; Roles

Endocytosis is a mechanism that internalizes membrane components and receptor-associated ligands through "endosomes", membrane-bound organelles. Upon dissociation of ligands, a large population of receptors returns to the plasma membrane via "recycling endosomes". While it is known that the acidic luminal pH of endosomes plays important roles in ligand-dissociation from the receptor and its degradation, our knowledge of recycling endosomal pH regulation, especially in neurons, is limited. The long-term goal of our research is to define biological roles of endosomal pH in neuronal cells. It is only very recently that researchers have begun to realize that endosomes are functionally more diverse in neurons than in non-neuronal cells, and proteins and lipids are sorted to axons and dendrites through those specialized endosomes. However, how the endosomal diversity is established in neuronal cells remains unknown. We hypothesize that neurons contain more acidic endosomes than non-neuronal cells, which provides a basis for preferential targeting of selected receptors to axons and dendrites. Thus, endosomal pH may add a new mechanistic insight into neuronal communication through the neurotransmitter and its receptor.

内吞作用是通过“内体”（膜结合细胞器）内化膜组分和受体相关配体的机制。在配体解离后，大量受体通过“再循环内体”返回质膜。虽然已知内体的酸性内腔pH在配体从受体解离及其降解中起重要作用，但我们对再循环内体pH调节（特别是在神经元中）的知识是有限的。我们研究的长期目标是确定内体pH在神经元细胞中的生物学作用。直到最近，研究人员才开始意识到，与非神经元细胞相比，神经元中的内体在功能上更加多样化，蛋白质和脂质通过这些专门的内体被分选到轴突和树突。然而，内体多样性如何在神经元细胞中建立仍然是未知的。我们假设神经元含有比非神经元细胞更多的酸性内体，这为选择性受体优先靶向轴突和树突提供了基础。因此，内体pH值可能会增加一个新的机制，通过神经递质及其受体的神经元通信的见解。