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

内吞作用是一种通过内吞体内膜结合细胞器内化膜成分和受体相关配体的机制。当配体解离时，大量受体通过“循环内小体”返回质膜。虽然已知内小体的酸性管腔pH在配体从受体解离及其降解中起重要作用，但我们对内小体再循环pH调节的了解有限，尤其是在神经元中。我们研究的长期目标是确定神经细胞内体pH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，神经元中的内小体在功能上更加多样化，蛋白质和脂类通过这些专门的内小体被分选到轴突和树突。然而，神经细胞中内体多样性是如何建立的仍不清楚。我们假设神经元比非神经元细胞含有更多的酸性内小体，这为选择性靶向轴突和树突的受体提供了基础。因此，内体pH可能通过神经递质及其受体增加对神经元通讯的新的机械性见解。

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.