title: Molecular identification and characterization of an essential pyruvate transporter from Trypanosoma brucei.
abstract: Pyruvate export is an essential physiological process for the bloodstream form of Trypanosoma brucei as the parasite would otherwise accumulate this end product of glucose metabolism to toxic levels. In the studies reported here, genetic complementation in Saccharomyces cerevisiae has been employed to identify a gene (TbPT0) that encodes this vital pyruvate transporter from T. brucei. Expression of TbPT0 in S. cerevisiae reveals that TbPT0 is a high affinity pyruvate transporter. TbPT0 belongs to a clustered multigene family consisting of five members, whose expression is up-regulated in the bloodstream form. Interestingly, TbPT family permeases are related to polytopic proteins from plants but not to characterized monocarboxylate transporters from mammals. Remarkably, inhibition of the TbPT gene family expression in bloodstream parasites by RNAi is lethal, confirming the physiological relevance of these transporters. The discovery of TbPT0 reveals for the first time the identity of the essential pyruvate transporter and provides a potential drug target against the mammalian life cycle stage of T. brucei.
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, Oregon 97239. Electronic address: sanchezm@ohsu.edu.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Sanchez
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001692:Biological Transport; D002264:Carboxylic Acids / Q000378:metabolism; D016923:Cell Death; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D005786:Gene Expression Regulation; D005816:Genetic Complementation Test; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D027501:Monocarboxylic Acid Transporters; D010802:Phylogeny; D015800:Protozoan Proteins / Q000378:metabolism*; D034622:RNA Interference; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014346:Trypanosoma brucei brucei / Q000378:metabolism*
chemical_list: D002264:Carboxylic Acids; D018076:DNA, Complementary; D026901:Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; D015800:Protozoan Proteins
keywords: Cell Death; Drug Target; Parasite Metabolism; Pyruvate; Transport; Trypanosoma brucei