遗传 ›› 2019, Vol. 41 ›› Issue (6): 451-468.doi: 10.16288/j.yczz.19-124

• 特邀综述 •    下一篇

细胞内吞循环运输通路及其分子调控机制

林珑,史岸冰   

  1. 1. 华中科技大学,同济医学院,基础医学院,生物化学与分子生物学系,武汉 430030
    2. 华中科技大学,脑研究所,武汉 430030
    3. 华中科技大学,同济医学院,教育部神经疾病重点实验室,武汉 430030
  • 收稿日期:2019-05-06 修回日期:2019-06-03 出版日期:2019-06-20 发布日期:2019-06-06
  • 作者简介:史岸冰,华中科技大学同济医学院教授,入选教育部“新世纪优秀人才支持计划”和国家“青年千人计划”,2018年获国家杰出青年科学基金资助。1996年毕业于南开大学,获学士学位;2010年毕业于美国新泽西州立Rutgers大学分子遗传学系,获理学博士学位;2010~2012年在美国斯坦福大学生物学系接受博士后训练。2013年受聘于华中科技大学同济医学院,主要从事极性真核细胞中囊泡循环运输调控网络的分子基础鉴定、分子调控过程及其时空特征解析等方面的研究。以模式生物秀丽线虫为研究模型,应用遗传学、生物化学及细胞生物学方法,围绕参与循环运输的重要基因筛选、新基因分子功能机制、循环运输相关磷酸肌醇代谢和细胞骨架动态等开展原创性研究,取得了一系列新进展。相关研究成果发表在J Cell Biol、EMBO J、PLoS Genet、PNAS、Curr Biol和Mol Biol Cell等国际著名细胞生物学期刊。|林珑,博士,副教授,研究方向：细胞内物质运输调控。E-mail: longlin@hust.edu.cn
  • 基金资助:
    国家杰出青年科学基金项目资助(31825017)

Endocytic recycling pathways and the regulatory mechanisms

Long Lin,Anbing Shi   

  1. 1. Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
    2. Institute for Brain Research, Huazhong University of Science and Technology, Wuhan 430030, China
    3. Key Laboratory of Neurological Disease of National Education Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
  • Received:2019-05-06 Revised:2019-06-03 Online:2019-06-20 Published:2019-06-06
  • Supported by:
    Supported by the National Science Fund for Distinguished Young Scholars(31825017)

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摘要：

内吞运输对于细胞与外界的物质信息交流至关重要,其过程涉及对胞外大分子、膜磷脂、膜蛋白内吞及分选的精细调控。在内吞运输系统中,循环运输通路负责将膜蛋白和磷脂等送回质膜,维持质膜组成的稳定,保障多种细胞生物学过程的正常进行,如营养吸收、细胞极性形成、细胞迁移、细胞分裂、突触可塑性、免疫应答、生长因子受体调控等。真核细胞中存在两大类循环运输通路,分别是网格蛋白依赖内吞货物蛋白的循环运输(CDE货物循环)和非网格蛋白依赖内吞货物蛋白的循环运输(CIE货物循环)。在体内具有重要生理功能的转铁蛋白受体TfR和低密度脂蛋白受体LDLR是CDE循环的代表性货物膜蛋白。近年,受CIE货物循环调控的重功能膜蛋白被逐步发现,如IL2 受体α-亚基、主要组织相容性复合体MHC ClassⅠ、葡萄糖转运因子GLUT4等。因而,对CIE货物循环调控机制的研究越来越受到学界关注,相关研究既有重要的细胞生物学理论意义,也能为诸如Ⅱ型糖尿病和癌症等重大疾病的诊疗策略提供科学依据和潜在治疗线索。相较于CDE货物循环,学界对CIE货物循环的研究开展较晚,对其调控机制的了解也较少。为此,本文在介绍内吞循环运输通路类型及其特点的基础上,着重关注CIE循环运输调控的分子基础,对CIE货物循环研究领域的新进展、新研究体系进行了归纳和说明。

关键词: 内吞循环运输, 网格蛋白依赖性内吞, 非网格蛋白依赖性内吞, 循环内体, Rab蛋白, Arf蛋白, 磷酸肌醇, 微丝, 秀丽隐杆线虫

Abstract:

Endocytic transport is imperative for the exchange of information between cells and the external environment. Specifically, the process of endocytic transport comprises precise regulation of uptake and sorting of extracellular macromolecules, phospholipids, and membrane proteins. In the endocytic transport system, the recycling pathways are responsible for delivering membrane proteins and phospholipids back to the plasma membrane. Thus, endocytic recycling plays critical roles in various biological processes, including nutrient absorption, cell polarity establishment, cell migration, cell division, synaptic plasticity, immune response, and growth factor receptor regulation. There are two essential types of recycling pathways in eukaryotic cells, recycling of clathrin-dependent endocytic cargos (CDE recycling) and recycling of clathrin-independent endocytic cargos (CIE recycling). The transferrin receptor TfR and the low-density lipoprotein receptor LDLR, which have essential physiological roles in vivo, are representative membrane proteins of the CDE recycling transport. In recent years, various membrane proteins governed by CIE recycling transport have been identified, including IL2 receptor α-subunit, major histocompatibility complex MHC Class I, and glucose transporter GLUT4. Therefore, the investigation of the regulatory mechanisms of CIE recycling has drawn notable attention in the field. Moreover, CIE recycling research presents fundamental significance in cell biology, which also provides scientific evidence and potential therapeutic clues for the diagnosis and treatment strategies of diseases such as type Ⅱ diabetes and cancer. Compared with the CDE recycling, the study on CIE recycling started later, and there is much to be learned of its regulatory mechanisms. To this end, this review summarizes the features of endocytic recycling pathways, focuses on the molecular basis of CIE recycling regulation and elaborates on the latest progress and newly developed research model systems in the field of CIE recycling.

Key words: endocytic recycling, clathrin-dependent endocytosis, clathrin-independent endocytosis, recycling endosome, Rab, Arf, phosphoinositide, F-actin, Caenorhabditis elegans