Christianson Helena C, Belting Mattias
Department of Clinical Sciences, Section of Oncology, Lund University, Lund, Sweden.
Department of Clinical Sciences, Section of Oncology, Lund University, Lund, Sweden; Skåne University Hospital & Oncology Clinic, Lund, Sweden.
Matrix Biol. 2014 Apr;35:51-5. doi: 10.1016/j.matbio.2013.10.004. Epub 2013 Oct 18.
How various macromolecules are exchanged between cells and how they gain entry into recipient cells are fundamental questions in cell biology with important implications e.g. non-viral drug delivery, infectious disease, metabolic disorders, and cancer. The role of heparan sulfate proteoglycan (HSPG) as a cell-surface receptor of diverse macromolecular cargo has recently been manifested. Exosomes, cell penetrating peptides, polycation-nucleic acid complexes, viruses, lipoproteins, growth factors and morphogens among other ligands enter cells through HSPG-mediated endocytosis. Key questions that partially have been unraveled over recent years include the respective roles of HSPG core protein and HS chain structure specificity for macromolecular cargo endocytosis, the down-stream intracellular signaling events involved in HSPG-dependent membrane invagination and vesicle formation, and the biological significance of the HSPG transport pathway. Here, we discuss the intriguing role of HSPGs as a major entry pathway of macromolecules in mammalian cells with emphasis on recent in vitro and in vivo data that provide compelling evidence of HSPG as an autonomous endocytosis receptor.
各种大分子如何在细胞间交换以及它们如何进入受体细胞是细胞生物学中的基本问题，在非病毒药物递送、传染病、代谢紊乱和癌症等领域具有重要意义。硫酸乙酰肝素蛋白聚糖（HSPG）作为多种大分子货物的细胞表面受体的作用最近已得到证实。外泌体、细胞穿透肽、聚阳离子-核酸复合物、病毒、脂蛋白、生长因子和形态发生素等配体通过HSPG介导的内吞作用进入细胞。近年来部分得到解答的关键问题包括HSPG核心蛋白和HS链结构特异性在大分子货物内吞作用中的各自作用、HSPG依赖性膜内陷和囊泡形成所涉及的下游细胞内信号事件，以及HSPG转运途径的生物学意义。在此，我们讨论HSPG作为哺乳动物细胞中大分子主要进入途径的有趣作用，重点是最近的体外和体内数据，这些数据提供了令人信服的证据证明HSPG是一种自主内吞受体。
