Stage-specific MCM protein expression in Trypanosoma cruzi: insights into metacyclogenesis and G1 arrested epimastigotes
Trypanosoma cruzi is a protozoan parasite that is the etiological agent of Chagas disease, which is endemic to Latin America with reported cases in non-endemic regions such as Europe, Asia, and Oceania due to migration. During its lifecycle, T. cruzi alternates between replicative and non-replicativ...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1584812/full |
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| author | Bruno Alves Santarossa Évelin Mariani Artur da Paixão Corrêa Fernanda C. Costa Martin C. Taylor John M. Kelly Maria Carolina Elias Simone Guedes Calderano |
| author_facet | Bruno Alves Santarossa Évelin Mariani Artur da Paixão Corrêa Fernanda C. Costa Martin C. Taylor John M. Kelly Maria Carolina Elias Simone Guedes Calderano |
| author_sort | Bruno Alves Santarossa |
| collection | DOAJ |
| description | Trypanosoma cruzi is a protozoan parasite that is the etiological agent of Chagas disease, which is endemic to Latin America with reported cases in non-endemic regions such as Europe, Asia, and Oceania due to migration. During its lifecycle, T. cruzi alternates between replicative and non-replicative infective lifeforms. Metacyclogenesis is the most studied transition of the T. cruzi life cycle, where replicative epimastigotes differentiate into infective metacyclic trypomastigotes inside the gut of the triatomine vector. This early-branching organism expresses a divergent pre-replication complex (pre-RC) where the only conserved component is the MCM2–7 protein family. Given the role of pre-RC components in cell cycle regulation, we investigated whether MCM expression and location could be involved in proliferation control in epimastigotes and during metacyclogenesis. Using CRISPR/Cas9, we tagged MCM subunits and tracked their expression and subcellular localization. Our findings reveal that MCM subunits are consistently expressed and localized to the nucleus throughout the epimastigote cell cycle, including in G1/G0-arrested cells. However, MCM subunits are degraded during metacyclogenesis as cells enter the G0 state, marking the transition to replication arrest. Therefore, epimastigotes arrested in G1/G0 can either maintain MCM complex expression and resume the cell cycle when conditions become favorable, or they can undergo metacyclogenesis, exiting the cell cycle and entering a G0 state, where MCM subunits are degraded as part of the replication repression mechanism. |
| format | Article |
| id | doaj-art-ceacdb687f10458da6570c5331c149f1 |
| institution | Kabale University |
| issn | 2235-2988 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj-art-ceacdb687f10458da6570c5331c149f12025-08-20T03:48:23ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-05-011510.3389/fcimb.2025.15848121584812Stage-specific MCM protein expression in Trypanosoma cruzi: insights into metacyclogenesis and G1 arrested epimastigotesBruno Alves Santarossa0Évelin Mariani1Artur da Paixão Corrêa2Fernanda C. Costa3Martin C. Taylor4John M. Kelly5Maria Carolina Elias6Simone Guedes Calderano7Cell Cycle Laboratory, Butantan Institute, São Paulo, BrazilCell Cycle Laboratory, Butantan Institute, São Paulo, BrazilCell Cycle Laboratory, Butantan Institute, São Paulo, BrazilDepartment of Infection Biology, London School of Hygiene and Tropical Medicine, London, United KingdomDepartment of Infection Biology, London School of Hygiene and Tropical Medicine, London, United KingdomDepartment of Infection Biology, London School of Hygiene and Tropical Medicine, London, United KingdomCell Cycle Laboratory, Butantan Institute, São Paulo, BrazilCell Cycle Laboratory, Butantan Institute, São Paulo, BrazilTrypanosoma cruzi is a protozoan parasite that is the etiological agent of Chagas disease, which is endemic to Latin America with reported cases in non-endemic regions such as Europe, Asia, and Oceania due to migration. During its lifecycle, T. cruzi alternates between replicative and non-replicative infective lifeforms. Metacyclogenesis is the most studied transition of the T. cruzi life cycle, where replicative epimastigotes differentiate into infective metacyclic trypomastigotes inside the gut of the triatomine vector. This early-branching organism expresses a divergent pre-replication complex (pre-RC) where the only conserved component is the MCM2–7 protein family. Given the role of pre-RC components in cell cycle regulation, we investigated whether MCM expression and location could be involved in proliferation control in epimastigotes and during metacyclogenesis. Using CRISPR/Cas9, we tagged MCM subunits and tracked their expression and subcellular localization. Our findings reveal that MCM subunits are consistently expressed and localized to the nucleus throughout the epimastigote cell cycle, including in G1/G0-arrested cells. However, MCM subunits are degraded during metacyclogenesis as cells enter the G0 state, marking the transition to replication arrest. Therefore, epimastigotes arrested in G1/G0 can either maintain MCM complex expression and resume the cell cycle when conditions become favorable, or they can undergo metacyclogenesis, exiting the cell cycle and entering a G0 state, where MCM subunits are degraded as part of the replication repression mechanism.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1584812/fullMini-Chromosome MaintenanceMCMTrypanosoma cruzimetacyclogenesisreplication controlG0 |
| spellingShingle | Bruno Alves Santarossa Évelin Mariani Artur da Paixão Corrêa Fernanda C. Costa Martin C. Taylor John M. Kelly Maria Carolina Elias Simone Guedes Calderano Stage-specific MCM protein expression in Trypanosoma cruzi: insights into metacyclogenesis and G1 arrested epimastigotes Frontiers in Cellular and Infection Microbiology Mini-Chromosome Maintenance MCM Trypanosoma cruzi metacyclogenesis replication control G0 |
| title | Stage-specific MCM protein expression in Trypanosoma cruzi: insights into metacyclogenesis and G1 arrested epimastigotes |
| title_full | Stage-specific MCM protein expression in Trypanosoma cruzi: insights into metacyclogenesis and G1 arrested epimastigotes |
| title_fullStr | Stage-specific MCM protein expression in Trypanosoma cruzi: insights into metacyclogenesis and G1 arrested epimastigotes |
| title_full_unstemmed | Stage-specific MCM protein expression in Trypanosoma cruzi: insights into metacyclogenesis and G1 arrested epimastigotes |
| title_short | Stage-specific MCM protein expression in Trypanosoma cruzi: insights into metacyclogenesis and G1 arrested epimastigotes |
| title_sort | stage specific mcm protein expression in trypanosoma cruzi insights into metacyclogenesis and g1 arrested epimastigotes |
| topic | Mini-Chromosome Maintenance MCM Trypanosoma cruzi metacyclogenesis replication control G0 |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2025.1584812/full |
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