自发性钙振荡调控星形胶质细胞突起极性生长的功能和分子机制研究

星形胶质细胞通过细长突起与神经和血管网络紧密接触，在神经环路形成及其功能维持中扮演重要角色。然而，星形胶质细胞突起极性生长的分子机制尚不明确。前期研究中，通过建立基于生理水平的钙操控方法和实现钙信号量化分析，我们发现，主要发生于突起部位的星形胶质细胞自发性钙振荡来源于内质网的钙释放，并能通过调控Protrudin和FYCO1/Rab7的互作，促进内体/溶酶体的外周运输。本项目将基于团队前期结果，通过钙信号量化分析和活细胞高分辨成像，结合细胞生化学分析，进一步研究自发性钙振荡调控的内体转运在胶质细胞突起形成中的作用。项目研究结果将初步揭示星形胶质细胞突起的形成过程及其极性生长的分子机制，为深入认识星形胶质细胞的生理功能，理解复杂神经网络环路的建立和相关疾病的发生机理，提供重要的理论参考。

Astrocytes, a major type of glial cells, are in close contact with both neurons and vasculature via their long fine processes, thus astroglial network, neuronal units together with brain vascular system form neuronal circuits which are essential for brain function. However, the underlying molecular mechanism of astrocytic process growth remains incompletely understood. Based on our established signal manipulation tool and calcium signal quantification algorithm, preliminary data showed that spontaneous calcium oscillation originates from ER, and promotes the peripheral translocation of endosomes/lysosomes via upregulating Protrudin interaction with FYCO1 and Rab7. With the combination of calcium signal quantification, high-resolution live cell imaging, and cytochemistry, our ongoing studies aim to elucidate the regulatory mechanism of spontaneous calcium oscillation on endosomal translocation, and its role in astrocytic process growth. By deciphering how processes are formed in astrocytes, this project will improve our understanding of astrocytic physiological functions, unravel the complexity of neuronal networks and provide a clue towards the pathogenesis of neuronal diseases.