Leucocytes中Coronin 1信号通路的时空调节机制研究

Coronin1是含有色氨酸-天冬氨酸（Tryp-Asp）重复序列的蛋白家族成员之一，特异的表达在Leucocytes中，位于细胞皮层骨架。Coronin1的已知功能为调节结核杆菌在巨噬细胞中的生存以及外周T细胞的存活。然而关于Coronin1蛋白在Leucocytes中的正常功能以及参与的信号通路基本上不清楚。Pieters实验室的最新研究结果发现Coronin1主要参与钙信号相关的信号通路的调节。为了更好的懂得Coronin1蛋白的正常生理功能，本研究将主要分析Coronin1相关信号在白细胞中的时间和空间调节机制。包括以下的几个主要方面：（1）鉴定在正常的白细胞中与Coronin1相互作用的蛋白；（2）通过活细胞成像技术研究Coronin1的定位动力学/时空分布信息，以及Coronin1参与的局域钙信号调节的时空信息；（3）分析转录后修饰对Coronin1蛋白的定位、功能的影响。

Coronin 1, a WD repeat protein family member, is exclusively expressed in Leucocytes, where it co-localizes with the cortical cytoskeleton. Coronin 1 is responsible for the intracellular survival of M.tuberculosis in macrophages as well as for the survival of T cells in periphery. While the exactly functions of Coronin 1 in lecucocytes remain largerly unclear. Recent studies from the Pieters' laboratory suggests that coronin 1 is involved in the modulation of Ca2+dependent signaling processes in leucocytes. To better understand the biological functions of coronin 1 in leukocytes, the planned research aims to analyse the temporal and spatial regulation of coronin 1 signaling in leukocytes. It will specifically focus on the following topics: (1), identify interaction partners of coronin 1 in normal leukocytes; (2), investigate localization dynamics of coronin 1 and coronin 1-dependent local calcium signaling by live cell imaging techniques; (3), analyze posttranslational modifications that may influence coronin 1 localization/function. Hence, this study will provide novel insight in the exact biological functions and biophysical properties of coronin 1 in leukocytes, and reveal how coronin 1-based signaling processes are being regulated.