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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
ADP-Ribosylation Factor 1 / deficiency
-
ADP-Ribosylation Factor 1 / genetics
-
ADP-Ribosylation Factor 1 / metabolism*
-
ADP-Ribosylation Factor 6
-
ADP-Ribosylation Factors / metabolism
-
Amino Acid Sequence
-
Animals
-
Cell Membrane / metabolism
-
Cell Survival
-
Down-Regulation
-
Endocytosis*
-
Exocytosis
-
Gene Expression
-
Golgi Apparatus / metabolism*
-
Guanosine Triphosphate / metabolism
-
Humans
-
Lysosomes / metabolism*
-
Microbodies / metabolism
-
Mutant Proteins / metabolism
-
Protein Transport
-
RNA Interference
-
Trypanosoma brucei brucei / cytology
-
Trypanosoma brucei brucei / metabolism*
-
Trypanosoma brucei brucei / ultrastructure
-
Variant Surface Glycoproteins, Trypanosoma / metabolism
Substances
-
ADP-Ribosylation Factor 6
-
Mutant Proteins
-
Variant Surface Glycoproteins, Trypanosoma
-
Guanosine Triphosphate
-
ADP-Ribosylation Factor 1
-
ADP-Ribosylation Factors
-
ARF6 protein, human