title: Trypanosoma brucei ARF1 plays a central role in endocytosis and golgi-lysosome trafficking.
abstract: The ADP ribosylation factor (Arf)1 orthologue in the divergent eukaryote Trypanosoma brucei (Tb) shares characteristics with both Arf1 and Arf6 and has a vital role in intracellular protein trafficking. TbARF1 is Golgi localized in trypanosomes but associates with the plasma membrane when expressed in human cells. Depletion of TbARF1 by RNA interference causes a major decrease in endocytosis, which correlates with Rab5 dissociation from early endosomes. Although the Golgi remains intact, parasites display enlarged flagellar pockets and intracellular flagella. An increase in active GTP-bound TbARF1 in bloodstream parasites is rapidly lethal, correlating with a defect in Golgi-to-lysosome transport. We conclude that the essential Golgi-localizing T. brucei ARF1 has a primary role in the maintenance of both post-Golgi transport and endocytosis and that it is significantly divergent from other characterized ARFs.
authors.affiliation: Immunology and Infection Unit, Department of Biology, University of York, Heslington, York YO10 5YW, United Kingdom.
authors.forename: Helen P
authors.initials: HP
authors.lastname: Price
authors.forename: Meg
authors.initials: M
authors.lastname: Stark
authors.forename: Deborah F
authors.initials: DF
authors.lastname: Smith
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D015536:Down-Regulation; D004705:Endocytosis; D005089:Exocytosis; D015870:Gene Expression; D006056:Golgi Apparatus / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008830:Microbodies / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D021381:Protein Transport; D034622:RNA Interference; D014346:Trypanosoma brucei brucei / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000378:metabolism
chemical_list: D000089982:ADP-Ribosylation Factor 6; D050505:Mutant Proteins; D014643:Variant Surface Glycoproteins, Trypanosoma; D006160:Guanosine Triphosphate; D020823:ADP-Ribosylation Factor 1; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human