Glyceraldehyde 3-phosphate dehydrogenase-telomere association correlates with redox status in Trypanosoma cruzi

PloS One
Ricardo Pariona-LlanosMaria Carolina Elias

Abstract

Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a classical metabolic enzyme involved in energy production and plays a role in additional nuclear functions, including transcriptional control, recognition of misincorporated nucleotides in DNA and maintenance of telomere structure. Here, we show that the recombinant protein T. cruzi GAPDH (rTcGAPDH) binds single-stranded telomeric DNA. We demonstrate that the binding of GAPDH to telomeric DNA correlates with the balance between oxidized and reduced forms of nicotinamide adenine dinucleotides (NAD+/NADH). We observed that GAPDH-telomere association and NAD+/NADH balance changed throughout the T. cruzi life cycle. For example, in replicative epimastigote forms of T. cruzi, which show similar intracellular concentrations of NAD+ and NADH, GAPDH binds to telomeric DNA in vivo and this binding activity is inhibited by exogenous NAD+. In contrast, in the T. cruzi non-proliferative trypomastigote forms, which show higher NAD+ concentration, GAPDH was absent from telomeres. In addition, NAD+ abolishes physical interaction between recombinant GAPDH and synthetic telomere oligonucleotide in a cell free system, mimicking exogenous NAD+ that reduces GAPDH-telomere interaction in vivo. We...Continue Reading

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Citations

Mar 5, 2016·Parallel Computing·Zhihao Lou, John Reinitz
Nov 12, 2015·International Journal of Molecular Sciences·Gaëlle Savreux-LengletMarie-Hélène David-Cordonnier
Nov 18, 2016·Molecular & Cellular Proteomics : MCP·Teresa Cristina Leandro de JesusJulia Pinheiro Chagas da Cunha
Oct 19, 2017·The Journal of Eukaryotic Microbiology·Raphael Souza PavaniMaria Carolina Elias
Apr 26, 2019·Current Drug Targets·Vilma G Duschak
Jun 14, 2016·Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics·Zhi-Jian WangYao-Guang Zhang

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Methods Mentioned

BETA
Immunoprecipitation
electrophoretic mobility shift assay
immunoprecipitation assay
nuclear translocation

Software Mentioned

MATLAB
Sundials library for C
Cell R
ImageJ

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