环境中稀土元素(REEs)富集于植物。植物叶细胞中REEs的靶分子，即被细胞质膜表面糖基磷脂酰肌醇(GPI)锚定在质膜外的阿拉伯半乳糖蛋白(AGPs)，启动了网格蛋白介导的胞吞作用(CME)，打破了叶细胞胞吞惰性的进化规则。已被生物学定义为分泌型蛋白且被GPI锚在质膜外的AGPs，是否及如何与质膜内各衔接蛋白复合而启动CME的胞吞途径等关键问题，亟待回答。项目以环境中累积量高的REEs(La、Ce、Tb)、经济作物大豆和模式植物拟南芥为代表；以揭示叶细胞中REEs靶分子AGPs启动不同胞吞途径为研究目的；以化学、细胞及分子生物学等研究方法为手段；以叶细胞对不同形态(剂量)REEs吸收→AGPs与不同衔接蛋白复合→不同胞吞途径启动→细胞及植物生长响应之间关系为研究内容；从细胞及分子水平阐明REEs靶分子AGPs启动叶细胞不同胞吞途径的植物效应机制，为建立REEs在食用植物中限量标准提供参考。

Rare earth elements (REEs) are widely used in agriculture, industry, national defense, and medicine, etc. For decades, REEs have been included in fertilizers for the improvement of plant growth and crop yields, but the mechanisms for REE entrance into plant cells and for their growth promotive effects remain poorly characterized. On the other hand, the widespread applications of REEs have resulted in the massive accumulation of REEs in the global environment and living organisms in an unprecedented speed. Therefore, the pollution of REEs is rapidly emerging as a universal threat to ecological integrity and function as well as the human health, highlighting the urgent need for establishing guidelines for limiting REEs in the ecosystem. To accomplish this goal, it is imperative that we have a clear qualitative and quantitative description about how REEs uptake by and act on plant cells. . Plants, as the primary producers of ecosystem, maintained the unique inactivity in endocytosis of leaf cells by the long-term evolution, which helps leaf to inhibit the penetration of exogenous harmful substances. Meanwhile, REEs, as nonessential elements for organisms, have accumulated in plant leaves. Results from our experiments in the project supported by Natural Science Foundation of China (21371100) indicated that the primary target of REEs in leaf cells, namely arabinogalactan proteins (AGPs) anchored outside the plasmic membrane (PM) by glycosyl phosphatidyl inositol (GPI), activated clathrin-mediated endocytosis (CME) of the leaf cells by breaking the long formed endocytosis inertia of the leaf cells. However, AGPs are biologically defined as a class of secretory proteins. That means AGPs cannot serve as cargos (i.e., transmembrane receptor proteins) to initiate the endocytosis in plant cells because the cargo must be transmembrane receptor protein and contain transmembrane domain. Surprisingly, we found that AGPs can flip-flip to the inner side of PM in Arabidopsis leaf cells in the present of REE(III) to activate and initiate CME of the leaf cells. Obviously, our findings “challenge long-established ideas about AGPs that are GPI–anchored proteins, and totally updates our traditional knowledge about AGPs” (from comments in Cell). However, some scientific issues urgently need to be solved. Based on biological principles, AGPs flipped to the inner side of PM are only possible to initiate and activate CME in leaf cells after forming complexes with intracellular adaptors in the inner side of the PM. The different complexes formed with intracellular different adaptors [such as adaptor protein 2 complex (AP2), or TPLATE complex (TPC), etc.] will initiate and activate different endocytic pathways of CME in plants. Especially how to initiate different endocytic pathways with different adaptors remains unknown, which is crucial to reveal the mechanism of REEs acting on plant cells. . The proposed project aims to reveal different endocytic pathways in plant leaf cells initiated by AGPs of the primary target of REEs (La, Ce, Tb) and their mechanisms. Meanwhile, model plant (Arabidopsis thaliana) and crop (soybean) will be chosen as a typical representative of plants, respectively. By using interdisciplinary techniques of rare earth chemistry, cytobiology, molecular biology, genetics, physical chemistry, etc., the relationship between different forms and doses of REEs→AGPs acting on different adaptors→the initiation of different endocytic pathways→the growth response of the plant cells to different endocytic pathways will be investigated. The mechanisms of plant effects caused by REEs (La, Ce, Tb) via AGPs initiating different endocytic pathways in leaf cells will be clarified at the cellular and molecular levels. These results would provide references for scientifically assessing food safety and risk of REEs in plants, and establishing the international standard of REEs limitation in edible plants.