Endocytosis and membrane receptor internalization: implication of F-BAR protein Carom.
Endocytosis and membrane receptor internalization: implication of F-BAR protein Carom.
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DOI：
10.2741/4552
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发表时间：
2017-03-01
期刊：
影响因子：
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通讯作者：
Wang H
中科院分区：
文献类型：
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作者：
Xu Y;Xia J;Liu S;Stein S;Ramon C;Xi H;Wang L;Xiong X;Zhang L;He D;Yang W;Zhao X;Cheng X;Yang X;Wang H
内吞作用是主要负责膜受体内化的细胞过程。细胞膜受体与其配体结合并形成可被内化的复合物。我们以前提出，F-BAR蛋白启动膜曲率和介导的内吞作用，通过其结合伙伴。然而，参与膜受体内吞作用的F-BAR蛋白伴侣及其调控机制仍不清楚。在本研究中，我们建立了一组数据库挖掘策略，以探索受体相关的内吞作用的机制。我们确定了34个内吞膜受体和10个调节蛋白的小泡形成网格蛋白依赖的内吞作用（CDE），膜受体内化的主要过程。我们发现F-BAR蛋白FCHSD 2（Carom）可以通过9个内吞伴侣促进内吞作用。Carom在内皮细胞和巨噬细胞中高表达，沿着高表达的内吞膜受体和配偶体。基于蛋白质-蛋白质相互作用和亚细胞定位，我们建立了三种Carom-受体复合物及其胞内转运模型。我们的结论是，Carom可能介导受体的内吞作用和运输内吞受体到细胞质的受体信号和溶酶体/蛋白酶体降解，或到细胞核的RNA加工，基因转录和DNA修复。
Endocytosis is a cellular process mostly responsible for membrane receptor internalization. Cell membrane receptors bind to their ligands and form a complex which can be internalized. We previously proposed that F-BAR protein initiates membrane curvature and mediates endocytosis via their binding partners. However, F-BAR protein partners involved in membrane receptor endocytosis and the regulatory mechanism remain unknown. In this study, we established a group of database mining strategies to explore mechanisms underlying receptor-related endocytosis. We identified 34 endocytic membrane receptors and 10 regulating proteins for vesicle formation in clathrin-dependent endocytosis (CDE), a major process of membrane receptor internalization. We found that F-BAR protein FCHSD2 (Carom) may facilitate endocytosis via 9 endocytic partners. Carom is highly expressed, along with highly expressed endocytic membrane receptors and partners, in endothelial cells and macrophages. We established 3 models of Carom-receptor complex and their intracellular trafficking based on protein-protein interaction and subcellular localization. We conclude that Carom may mediate receptor endocytosis and transport endocytic receptors to the cytoplasm for receptor signaling and lysosome/proteasome degradation, or to the nucleus for RNA processing, gene transcription and DNA repair.