Department of Membrane Biochemistry, Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195, Berlin, Germany.
Traffic. 2012 Apr;13(4):495-504. doi: 10.1111/j.1600-0854.2011.01292.x. Epub 2011 Oct 24.
Intracellular membrane traffic regulates cell physiology at multiple levels ranging from cell growth and development to the function of the nervous and immune systems. Multiple endocytic routes are used by distinct cargoes including ligands bound to their receptors but also viruses and pathogens to gain access to the cell interior. Within the endosomal system, proteins and lipids are sorted for degradation or recycling allowing cells to dynamically respond to environmental signals and to regulate cell shape and morphology. Some receptors or toxins are sorted along the retrograde pathway from endosomes to the Golgi complex, where they intersect with secretory cargo destined for exocytosis. Genetic manipulations of these pathways frequently cause problems with regard to data interpretation as the resulting phenotypes may be indirect consequences resulting from perturbation of multiple steps or trafficking routes. Hence, novel approaches are needed to acutely and reversibly perturb intracellular membrane traffic, e.g., by small molecule inhibitors. Such drugs may also be pharmacologically important as they offer new avenues to fight human diseases. Here, we provide an overview of the small molecules available to interfere with intracellular membrane traffic and outline strategies for future research.
细胞内膜运输在多个层面上调节细胞生理学，范围从细胞生长和发育到神经系统和免疫系统的功能。不同的货物（包括与其受体结合的配体，但也包括病毒和病原体）使用多种内吞途径进入细胞内部。在内体系统中，蛋白质和脂质被分拣用于降解或回收，使细胞能够动态响应环境信号并调节细胞形状和形态。一些受体或毒素沿着从内体到高尔基体复合物的逆行途径分拣，在那里它们与注定要分泌的分泌货物交叉。这些途径的遗传操作经常导致数据解释方面的问题，因为所产生的表型可能是由于对多个步骤或运输途径的干扰而产生的间接后果。因此，需要新的方法来急性和可逆地干扰细胞内膜运输，例如通过小分子抑制剂。这些药物也可能具有药理学上的重要性，因为它们为对抗人类疾病提供了新的途径。在这里，我们概述了可用于干扰细胞内膜运输的小分子，并概述了未来研究的策略。
