Author | Moreira, Claudia Maria do Nascimento | |
Author | Batista, Cassiano Martin | |
Author | Fernandes, Jessica Chimenes | |
Author | Kessler, Rafael Luis | |
Author | Soares, Maurilio José | |
Author | Fragoso, Stenio Perdigão | |
Access date | 2017-08-29T18:19:54Z | |
Available date | 2017-08-29T18:19:54Z | |
Document date | 2017 | |
Citation | MOREIRA, Claudia Maria do Nascimento et al. Knockout of the gamma subunit of the AP-1 adaptor complex in the human parasite Trypanosoma cruzi impairs infectivity and differentiation and prevents the maturation and targeting of the major protease cruzipain. PLoS ONE, v. 12, n. 7, 2017. | pt_BR |
ISSN | 0179615 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/20827 | |
Language | por | pt_BR |
Publisher | Public Library of Science | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Trypanosoma | pt_BR |
Title | Knockout of the gamma subunit of the AP-1 adaptor complex in the human parasite Trypanosoma cruzi impairs infectivity and differentiation and prevents the maturation and targeting of the major protease cruzipain | pt_BR |
Type | Article | pt_BR |
DOI | https://doi.org/10.1371/journal.pone.0179615 | |
Abstract | The AP-1 Adaptor Complex assists clathrin-coated vesicle assembly in the trans-Golgi network (TGN) of eukaryotic cells. However, the role of AP-1 in the protozoan Trypanosoma cruzi-the Chagas disease parasite-has not been addressed. Here, we studied the function and localization of AP-1 in different T. cruzi life cycle forms, by generating a gene knockout of the large AP-1 subunit gamma adaptin (TcAP1-γ), and raising a monoclonal antibody against TcAP1-γ. Co-localization with a Golgi marker and with the clathrin light chain showed that TcAP1-γ is located in the Golgi, and it may interact with clathrin in vivo, at the TGN. Epimastigote (insect form) parasites lacking TcAP1-γ (TcγKO) have reduced proliferation and differentiation into infective metacyclic trypomastigotes (compared with wild-type parasites). TcγKO parasites have also displayed significantly reduced infectivity towards mammalian cells. Importantly, TcAP1-γ knockout impaired maturation and transport to lysosome-related organelles (reservosomes) of a key cargo-the major cysteine protease cruzipain, which is important for parasite nutrition, differentiation and infection. In conclusion, the defective processing and transport of cruzipain upon AP-1 ablation may underlie the phenotype of TcγKO parasites. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. | pt_BR |
Subject | Transcription Factor AP-1 | pt_BR |
Subject | Parasites | pt_BR |
Subject in Spanish | Factor de Transcripción AP-1 | pt_BR |
Subject in Spanish | Parásitos | pt_BR |
DeCS | Fator de Transcrição AP-1 | pt_BR |
DeCS | Parasitos | pt_BR |