Department of Systems Biology, The University of Texas, MD Anderson Cancer Center, Houston, TX 77054-1942, USA.
Semin Cell Dev Biol. 2011 Feb;22(1):57-68. doi: 10.1016/j.semcdb.2010.12.005. Epub 2010 Dec 13.
The endocytotic machinery imports, transports and exports receptors and associated molecules between the plasma membrane and various cytoplasmic chambers resulting in selective recycling, degradation, or secretion of molecules and signaling complexes. Trafficking of receptors, growth factors, nutrients, cytokines, integrins as well as pathogens dictates the kinetics and magnitude of signal transduction cascades. Understandably, alterations in the 'fate' of such cargo complexes have profound physiologic and pathophysiologic implications. Rab GTPases regulate endocytosis by decorating intracellular vesicles and targeting these vesicles along with their cargoes to appropriate subcellular compartments. In the last decade, the number of genetic diseases driven by germline mutations in Rab GTPases or their interacting proteins, has increased and there is growing evidence of aberrant Rab GTPase function in acquired pathophysiologies such as immune deficiency, infection, obesity, diabetes and cancer.
内吞作用机制在质膜和各种细胞质室之间导入、运输和输出受体和相关分子，从而导致分子和信号复合物的选择性回收、降解或分泌。受体、生长因子、营养物质、细胞因子、整合素以及病原体的运输决定了信号转导级联的动力学和幅度。可以理解的是，这些货物复合物的“命运”的改变具有深远的生理和病理生理意义。RAB GTPases 通过修饰细胞内囊泡并将这些囊泡及其货物靶向到适当的亚细胞隔室来调节内吞作用。在过去的十年中，由 RAB GTPases 或其相互作用蛋白的种系突变驱动的遗传疾病的数量增加了，并且越来越多的证据表明，获得性病理生理学（如免疫缺陷、感染、肥胖、糖尿病和癌症）中存在异常的 RAB GTPase 功能。
