Homology, paralogy and function of DGF-1, a highly dispersed Trypanosoma cruzi specific gene family and its implications for information entropy of its encoded proteins

Kawashita, Silvia Y.; Silva, Cláudio V. da; Mortara, Renato Arruda; Burleigh, Barbara A.; Briones, Marcelo R. S.

doi:10.1016/j.molbiopara.2008.12.010

Cited by 32 publications

(60 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These facts and the absence of DGF-1 hits in the T. cruzi plasma membrane proteome (unpublished data) apparently contradict a recent report (15) suggesting a cell surface localization for DGF-1 in T. cruzi strain Y and G trypomastigotes. The authors of this work biotinylated trypomastigote cell surface proteins and used anti DGF-1 antibodies to detect streptavidin affinity-purified proteins.…”

Section: Downloaded Fromcontrasting

confidence: 61%

Localization and Developmental Regulation of a Dispersed Gene Family 1 Protein in Trypanosoma cruzi

et al. 2010

View full text Add to dashboard Cite

The dispersed gene family 1 (DGF-1) is the fifth largest gene family in the Trypanosoma cruzi genome, with over 500 members (11). Many of the predicted DGF-1 protein products have several transmembrane domains and N-glycosylation and phosphorylation sites and were thought to localize in the plasma membrane. Here, we report that affinity-purified antibodies against a region of one of these proteins (DGF-1.2) localized it intracellularly in different stages of the parasite. DGF-1.2 is more abundant in the amastigote stage than in trypomastigotes and epimastigotes, as detected by immunofluorescence and Western blot analyses. The protein changed localization during intracellular or extracellular differentiation from the trypomastigote to the amastigote stage, where it finally localized to small bodies in close contact with the inner side of the amastigote plasma membrane. DGF-1.2 did not colocalize with markers of other subcellular organelles, such as acidocalcisomes, glycosomes, reservosomes, lipid droplets, or endocytic vesicles. During extracellular differentiation, the protein was detected in the culture medium from 0 to 22 h, peaking at 14 h. The presence of DGF-1.2 in the differentiation culture medium was confirmed by mass spectrometry analysis. Finally, when epimastigotes were subjected to starvation, there was a decrease in the labeling of the cells and, in Western blots, the appearance of bands of lower molecular mass, suggesting its cleavage. These results represent the first report of direct immunodetection and developmental expression and secretion of a DGF-1 protein.Trypanosoma cruzi is the causative agent of Chagas disease, an endemic illness affecting between 16 and 18 million people in North, Central, and South America for which no vaccine or satisfactory treatment is available (22). During its life cycle, the parasite goes through different stages in the vector (epimastigotes and metacyclic trypomastigotes) and in the mammalian host (amastigotes and bloodstream trypomastigotes). As part of its survival strategy in these varying environments, the parasite has developed a large repertoire of multigene families (9,11,12,16). Among these families, the dispersed gene family 1 (DGF-1) has approximately 565 copies, ranging from 6 to 10 kbp, dispersed throughout the parasite genome (11). The members of the DGF-1 family encode proteins that share 85 to 95% sequence identity (11). Wincker and colleagues first identified clones bearing a common repeated sequence from a T. cruzi genome library (24) and later described the nucleotide sequence of a representative gene (DGF-1.1) (23). They concluded, from in silico studies, that DGF-1 genes encoded putative cell surface proteins (23). In 2005, Kim and colleagues (16) described a new member of this family (DGF-1.2) located in the subtelomeric region of a T. cruzi chromosome surrounded by mainly two kinds of sequences: genes encoding the trans-sialidase (TS) and retrotransposon hot spot (RHS) protein families. The sizes of the open reading frames (ORFs) of DGF-1 ge...

show abstract

Section: Downloaded Fromcontrasting

confidence: 61%

Localization and Developmental Regulation of a Dispersed Gene Family 1 Protein in Trypanosoma cruzi

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Most of the surface proteins belong to multigene families and are involved in the interaction with their hosts (De Pablos & Osuna, 2012). Several studies have been performed in the different protein groups aimed to shed light on their structure, post-translational modifications, their role in the infection and prevalence and the importance as markers or possible drug targets (Acosta-Serrano, Cole & Englund, 2000; Buscaglia, Campo & Frasch, 2006; De Pablos & Osuna, 2012; Freitas et al, 2011; Kawashita et al, 2009). The first T. cruzi genome studies have given a more integrative view of the complexity of these expanded families, and have even allowed the identification of a new protein family named Mucin-associated surface proteins (El-Sayed et al, 2005; Franzén et al, 2011; Franzén et al, 2012; Grisard et al, 2014).…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic analysis reveals metabolic switches and surface remodeling as key processes for stage transition inTrypanosoma cruzi

Berná

Chiribao

Greif

et al. 2017

PeerJ

View full text Add to dashboard Cite

American trypanosomiasis is a chronic and endemic disease which affects millions of people. Trypanosoma cruzi, its causative agent, has a life cycle that involves complex morphological and functional transitions, as well as a variety of environmental conditions. This requires a tight regulation of gene expression, which is achieved mainly by post-transcriptional regulation. In this work we conducted an RNAseq analysis of the three major life cycle stages of T. cruzi: amastigotes, epimastigotes and trypomastigotes. This analysis allowed us to delineate specific transcriptomic profiling for each stage, and also to identify those biological processes of major relevance in each state. Stage specific expression profiling evidenced the plasticity of T. cruzi to adapt quickly to different conditions, with particular focus on membrane remodeling and metabolic shifts along the life cycle. Epimastigotes, which replicate in the gut of insect vectors, showed higher expression of genes related to energy metabolism, mainly Krebs cycle, respiratory chain and oxidative phosphorylation related genes, and anabolism related genes associated to nucleotide and steroid biosynthesis; also, a general down-regulation of surface glycoprotein coding genes was seen at this stage. Trypomastigotes, living extracellularly in the bloodstream of mammals, express a plethora of surface proteins and signaling genes involved in invasion and evasion of immune response. Amastigotes mostly express membrane transporters and genes involved in regulation of cell cycle, and also express a specific subset of surface glycoprotein coding genes. In addition, these results allowed us to improve the annotation of the Dm28c genome, identifying new ORFs and set the stage for construction of networks of co-expression, which can give clues about coded proteins of unknown functions.

show abstract

“…This is the fifth largest gene family in the genome of T. cruzi and contains 565 genes and 136 pseudogenes (28). Many members of this family are located in subtelomeric chromosome regions where the variability in their sequences may be favored (39,40). According to its genealogy, the family can be divided into at least three groups, with phenomena of gene duplication, recombination, and hybridization that would stimulate the generation of diversity in terms of gene conversion (39).…”

mentioning

confidence: 99%

“…Many members of this family are located in subtelomeric chromosome regions where the variability in their sequences may be favored (39,40). According to its genealogy, the family can be divided into at least three groups, with phenomena of gene duplication, recombination, and hybridization that would stimulate the generation of diversity in terms of gene conversion (39). Bioinformatic studies of various T. cruzi gene families and multiple point mutation models over 1,000 generations have shown that this family has undergone a series of point mutations and shows the highest rate of variability in its sequences (9).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Multigene Families in Trypanosoma cruzi and Their Role in Infectivity

Pablos

Osuna

2012

Infect Immun

View full text Add to dashboard Cite

ABSTRACTTheTrypanosoma cruzigenome contains the most widely expanded content (∼12,000 genes) of the trypanosomatids sequenced to date. This expansion is reflected in the high number of repetitive sequences and particularly in the large quantity of genes that make up its multigene families. Recently it was discovered that the contents of these families vary between phylogenetically unrelated strains. We review the basic characteristics of trans-sialidases and mucins as part of the mechanisms of immune evasion ofT. cruziand as ligands and factors involved in the cross talk between the host cell and the parasite. We also show recently published data describing two new multigene families, DGF-1 and MASP, that form an important part of the scenario representing the complex biology ofT. cruzi.

show abstract

Homology, paralogy and function of DGF-1, a highly dispersed Trypanosoma cruzi specific gene family and its implications for information entropy of its encoded proteins

Cited by 32 publications

References 89 publications

Localization and Developmental Regulation of a Dispersed Gene Family 1 Protein in Trypanosoma cruzi

Localization and Developmental Regulation of a Dispersed Gene Family 1 Protein in Trypanosoma cruzi

Transcriptomic analysis reveals metabolic switches and surface remodeling as key processes for stage transition inTrypanosoma cruzi

Multigene Families in Trypanosoma cruzi and Their Role in Infectivity

Contact Info

Product

Resources

About