title: Rab GTPases, intracellular traffic and disease.
abstract: 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.
authors.affiliation: Cell and Molecular Biology, Division of Biomedical Sciences, Faculty of Medicine, Imperial College, Exhibition Road, London, UK SW7 2AZ. m.seabra@ic.ac.uk
authors.forename: Miguel C
authors.initials: MC
authors.lastname: Seabra
authors.forename: Emilie H
authors.initials: EH
authors.lastname: Mules
authors.forename: Alistair N
authors.initials: AN
authors.lastname: Hume
mesh_terms: D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D002874:Chromosome Mapping; D006801:Humans; D020460:Melanosomes / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D010587:Phagocytosis; D013577:Syndrome; D013601:T-Lymphocytes / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D000075745:rab27 GTP-Binding Proteins
chemical_list: D002352:Carrier Proteins; D000075745:rab27 GTP-Binding Proteins; C066694:RAB27A protein, human; C512962:Rab27a protein, mouse; D020691:rab GTP-Binding Proteins