Document Detail


Cationic amino acid uptake constitutes a metabolic regulation mechanism and occurs in the flagellar pocket of Trypanosoma cruzi.
MedLine Citation:
PMID:  22393446     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Trypanosomatids' amino acid permeases are key proteins in parasite metabolism since they participate in the adaptation of parasites to different environments. Here, we report that TcAAP3, a member of a Trypanosoma cruzi multigene family of permeases, is a bona fide arginine transporter. Most higher eukaryotic cells incorporate cationic amino acids through a single transporter. In contrast, T. cruzi can recognize and transport cationic amino acids by mono-specific permeases since a 100-fold molar excess of lysine could not affect the arginine transport in parasites that over-express the arginine permease (TcAAP3 epimastigotes). In order to test if the permease activity regulates downstream processes of the arginine metabolism, the expression of the single T. cruzi enzyme that uses arginine as substrate, arginine kinase, was evaluated in TcAAP3 epimastigotes. In this parasite model, intracellular arginine concentration increases 4-folds and ATP level remains constant until cultures reach the stationary phase of growth, with decreases of about 6-folds in respect to the controls. Interestingly, Western Blot analysis demonstrated that arginine kinase is significantly down-regulated during the stationary phase of growth in TcAAP3 epimastigotes. This decrease could represent a compensatory mechanism for the increase in ATP consumption as a consequence of the displacement of the reaction equilibrium of arginine kinase, when the intracellular arginine concentration augments and the glucose from the medium is exhausted. Using immunofluorescence techniques we also determined that TcAAP3 and the specific lysine transporter TcAAP7 co-localize in a specialized region of the plasma membrane named flagellar pocket, staining a single locus close to the flagellar pocket collar. Taken together these data suggest that arginine transport is closely related to arginine metabolism and cell energy balance. The clinical relevance of studying trypanosomatids' permeases relies on the possibility of using these molecules as a route of entry of therapeutic drugs.
Authors:
Mariana R Miranda; Melisa Sayé; León A Bouvier; María de Los Milagros Cámara; Javier Montserrat; Claudio A Pereira
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-02-29
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-03-06     Completed Date:  2012-07-23     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e32760     Citation Subset:  IM    
Affiliation:
Laboratorio de Biología Molecular de Trypanosoma cruzi (LBMTC), Instituto de Investigaciones Médicas Alfredo Lanari, Universidad de Buenos Aires and CONICET, Buenos Aires, Argentina.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / chemistry
Amino Acids / chemistry*
Arginine / genetics,  metabolism
Arginine Kinase / chemistry
Biological Transport
Cations / chemistry*
Computational Biology / methods
Down-Regulation
Flagella / physiology*
Humans
Lysine / metabolism
Microscopy, Fluorescence / methods
Plasmids / metabolism
Substrate Specificity
Trypanosoma cruzi / metabolism*,  physiology*
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Cations; 56-65-5/Adenosine Triphosphate; 56-87-1/Lysine; 74-79-3/Arginine; EC 2.7.3.3/Arginine Kinase
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