Seabra Miguel C, Mules Emilie H, Hume Alistair N
Cell and Molecular Biology, Division of Biomedical Sciences, Faculty of Medicine, Imperial College, Exhibition Road, London, UK SW7 2AZ.
Trends Mol Med. 2002 Jan;8(1):23-30. doi: 10.1016/s1471-4914(01)02227-4.
Membrane and protein traffic in the secretory and endocytic pathways is mediated by vesicular transport. Recent studies of certain key regulators of vesicular transport, the Rab GTPases, have linked Rab dysfunction to human disease. Mutations in Rab27a result in Griscelli syndrome, caused by defects in melanosome transport in melanocytes and loss of cytotoxic killing activity in Tcells. Other genetic diseases are caused by partial dysfunction of multiple Rab proteins resulting from mutations in general regulators of Rab activity; Rab escort protein-1 (choroideremia), Rab geranylgeranyl transferase (Hermansky-Pudlak syndrome) and Rab GDP dissociation inhibitor-alpha (X-linked mental retardation). In infectious diseases caused by intracellular microorganisms, the function of endocytic Rabs is altered either as part of host defences or as part of survival strategy of the pathogen. The human genome is predicted to contain 60 RAB genes, suggesting that future work could reveal further links between Rab dysfunction and disease.
分泌途径和内吞途径中的膜和蛋白质运输是由囊泡运输介导的。最近对囊泡运输的某些关键调节因子Rab GTP酶的研究表明，Rab功能障碍与人类疾病有关。Rab27a的突变会导致格里塞利综合征，这是由黑素细胞中黑素体运输缺陷和T细胞中细胞毒性杀伤活性丧失引起的。其他遗传疾病是由Rab活性的一般调节因子发生突变导致多种Rab蛋白部分功能障碍引起的；Rab护送蛋白-1（脉络膜视网膜病变）、Rab香叶基香叶基转移酶（赫尔曼斯基-普德拉克综合征）和Rab GDP解离抑制剂-α（X连锁智力迟钝）。在由细胞内微生物引起的传染病中，内吞Rab的功能会作为宿主防御的一部分或病原体生存策略的一部分而发生改变。预计人类基因组包含60个RAB基因，这表明未来的研究可能会揭示Rab功能障碍与疾病之间的更多联系。
