CEDOC, Faculdade de Ciências Médicas, FCM, Universidade Nova de Lisboa, 1169-056, Lisboa, Portugal.
Traffic. 2013 Aug;14(8):871-85. doi: 10.1111/tra.12072. Epub 2013 Apr 29.
Rab and ADP-ribosylation factor (Arf) family proteins are master regulators of membrane trafficking and are involved in all steps of vesicular transport. These families of small guanine-nucleotide-binding (G) proteins are well suited to regulate membrane trafficking processes since their nucleotide state determines their conformation and the capacity to bind to a multitude of effectors, which mediate their functions. In recent years, several inherited diseases have been associated with mutations in genes encoding proteins belonging to these two families or in proteins that regulate their GTP-binding cycle. The genetic diseases that are caused by defects in Rabs, Arfs or their regulatory proteins are heterogeneous and display diverse symptoms. However, these diseases mainly affect two types of subcellular compartments, namely lysosome-related organelles and cilia. Also, several of these diseases affect the nervous system. Thus, the study of these diseases represents an opportunity to understand their etiology and the molecular mechanisms involved, as well as to develop novel therapeutic strategies.
Rab 和 ADP-核糖基化因子（Arf）家族蛋白是膜运输的主要调节剂，参与囊泡运输的所有步骤。这些小 G 蛋白家族非常适合调节膜运输过程，因为它们的核苷酸状态决定了它们的构象和与多种效应物结合的能力，而这些效应物介导它们的功能。近年来，几种遗传性疾病与编码属于这两个家族的蛋白或调节其 GTP 结合循环的蛋白的基因突变有关。由 Rab、Arf 或其调节蛋白缺陷引起的遗传疾病具有异质性，并表现出不同的症状。然而，这些疾病主要影响两种类型的亚细胞区室，即溶酶体相关细胞器和纤毛。此外，这些疾病中的几种还会影响神经系统。因此，研究这些疾病为了解其病因和涉及的分子机制以及开发新的治疗策略提供了机会。
