ARVCF调节cadherin/catenin复合体介导的细胞间黏附的分子机制研究

项目名称： ARVCF调节cadherin/catenin复合体介导的细胞间黏附的分子机制研究

项目编号： No.81672302

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 张迪

作者单位： 中国医科大学

项目金额： 25万元

中文摘要： E-cad是一种跨膜蛋白，胞内区可形成E-cad/catenin复合体。p120ctn是Arm重复蛋白，可结合E-cad的JMDcore区，稳定E-cad/catenin复合体。解联p120ctn与JMDcore，将导致E-cad的内化。这主要与JMDcore旁的内化位点有关，p120ctn的C-端阻断了内化位点。ARVCF是p120ctn亚家族成员之一，可以与p120ctn竞争结合E-cad，导致E-cad内化。ARVCF的磷酸化可减弱E-cad内化。我们推测：ARVCF依靠1-5Arm与 JMDcore结合，但其C-端却不能封闭内化位点。而改变ARVCF的磷酸化，则可以开放或封闭E-cad的内化位点。我们计划利用NMR及X-ray检测ARVCF/E-cad复合体的三维结构，并构建ARVCF和E-cad的突变/剪接体，从分子空间结构角度，揭示ARVCF调控E-cad的分子机机制。

中文关键词： ARVCF；E-cadherin；p120ctn；磷酸化；内化

英文摘要： E-cad is a transmembrane protein, whose intracellular region forms E-cad/catenin complex. P120ctn is an Arm repeat protein which binds to the JMDcore of E-cad, and stabilizes E-cad/catenin complex. Uncoupling of p120ctn and JMDcore will lead to the internalization of E-cad. This is mainly related with the internalized motif beside the JMDcore,and C-terminus of p120ctn blocked the internalization motif. ARVCF is a member of p120ctn subfamily, and competes with p120ctn for binding to E-cadherin, resulting in the internalization of E-cad. The phosphorylation of ARVCF can reduce internalization of E-cad. We speculate that ARVCF binds to JMDcore by 1-5Arm,but the C-terminus of ARVCF cannot block the internalized motif. The change of phosphorylation of ARVCF, may open or close the internalization motif. We plan to detect three-dimensional structure of ARVCF/E-cad complex by NMR and X-ray, and construct mutation and spliceosome of ARVCF and E-cad, which reveal the molecular mechanism of ARVCF regulating E-cad from the point of view of molecular space structure.

英文关键词： ARVCF;E-cadherin;p120ctn;phosphorylation;internalization