SDPR和PTRF蛋白调控细胞膜弯曲的分子功能机制

SDPR and PTRF have been reported to be highly relevant to the caveolae function. However, our preliminary data have suggested that SDPR and/or PTRF perform far beyond caveolae itself on cell membrane. Several kinds of membrane curvature without caveolae even without PTRF were found to exist extensively in cell membrane. So we propose SDPR and/or PTRF were novel components of membrane tension machinery. In this project, we’ll investigate how SDPR and/or SDPR-PTRF mediate different membrane curvature formation, thus closely control cell membrane tension, cell motility, endocytosis and metabolic signal transduction. This project will provide more clues to many biological problems such as tumor cell metastasis, endocrine hormone secretion, energy metabolism and its signal control.

我们前期研究发现SDPR和PTRF除影响膜小窝的功能外，还广泛影响多种细胞膜皱褶的形成。本项目将深入研究SDPR、PTRF调控细胞膜张力、细胞膜的韧性和膜储备的分子机制：研究SDPR引发膜皱褶和SDPR-PTRF复合物相互作用引发特殊膜皱褶的分子机制；分析SDPR和PTRF在介导cavicle与质膜融合过程中的作用模式；阐明SDPR-PTRF引发的膜皱褶对细胞膜张力、内吞、细胞代谢信号传导和细胞运动的影响。本项目研究将阐明控制细胞膜张力的结构性要素和调控机制，有助于解答与癌细胞的迁移和浸润、内分泌激素的释放、脂肪等营养物质的转运和代谢等基本生命活动相关的膜生物学问题。

SDPR，PTRF除影响膜小窝的功能外，还影响细胞膜皱褶的形成。本项目研究鉴定了SDPR结合PTRF以及自身形成多聚体的结构域是aa61-82，而PTRF与自身以及结合SDPR的结构域是aa50-77；鉴定了PKC激酶磷酸化SDPR的位点为S234，该位点位于磷脂酰肌醇结合结构域aa203-282，该结构域能够识别和结合磷脂酰肌醇，其中结合PI5P最为显著；SDPR通过PKC的磷酸化调控其与细胞膜的结合。细胞内吞实验表明，SDPR过表达促进细胞内吞，而PTRF过表达抑制细胞内吞。这些研究结果进一步阐明了SDPR 与PTRF 复合物调控细胞膜弯曲的分子机制。