Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California 94143-0552, USA.
Annu Rev Cell Dev Biol. 2012;28:309-36. doi: 10.1146/annurev-cellbio-101011-155716. Epub 2012 Jul 23.
Clathrin is considered the prototype vesicle coat protein whose self-assembly mediates sorting of membrane cargo and recruitment of lipid modifiers. Detailed knowledge of clathrin biochemistry, structure, and interacting proteins has accumulated since the first observation, almost 50 years ago, of its role in receptor-mediated endocytosis of yolk protein. This review summarizes that knowledge, and focuses on properties of the clathrin heavy and light chain subunits and interaction of the latter with Hip proteins, to address the diversity of clathrin function beyond conventional receptor-mediated endocytosis. The distinct functions of the two human clathrin isoforms (CHC17 and CHC22) are discussed, highlighting CHC22's specialized involvement in traffic of the GLUT4 glucose transporter and consequent role in human glucose metabolism. Analysis of clathrin light chain function and interaction with the actin-binding Hip proteins during bacterial infection defines a novel actin-organizing function for CHC17 clathrin. By considering these diverse clathrin functions, along with intracellular sorting roles and influences on mitosis, further relevance of clathrin function to human health and disease is established.
网格蛋白被认为是囊泡包被蛋白的原型，其自组装介导了膜货物的分拣和脂质修饰物的募集。自大约 50 年前首次观察到网格蛋白在卵黄蛋白受体介导的胞吞作用中的作用以来，关于网格蛋白的生化、结构和相互作用蛋白的详细知识已经积累起来。这篇综述总结了这些知识，并重点介绍了网格蛋白重链和轻链亚基的特性以及后者与 Hip 蛋白的相互作用，以解决除传统受体介导的胞吞作用之外的网格蛋白功能的多样性。讨论了两种人类网格蛋白同工型（CHC17 和 CHC22）的不同功能，强调了 CHC22 专门参与 GLUT4 葡萄糖转运体的运输及其在人类葡萄糖代谢中的作用。在细菌感染过程中对网格蛋白轻链功能及其与肌动蛋白结合 Hip 蛋白的相互作用的分析，定义了 CHC17 网格蛋白的一种新的肌动蛋白组织功能。通过考虑这些不同的网格蛋白功能，以及细胞内分拣作用和对有丝分裂的影响，进一步确定了网格蛋白功能与人类健康和疾病的相关性。
