Depolymerization of SUMO chains induces slender to stumpy differentiation in T. brucei bloodstream parasites

Autores
Iribarren, Paula Ana; Di Marzio, Lucía Ayelén; Berazategui, Maria Agustina; Saura, Andreu; Coria, Mirta Lorena; Cassataro, Juliana; Rojas, Federico; Navarro, Miguel; Alvarez, Vanina Eder
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Trypanosoma brucei are protozoan parasites that cause sleeping sickness in humans and nagana in cattle. Inside the mammalian host, a quorum sensing-like mechanism coordinates its differentiation from a slender replicative form into a quiescent stumpy form, limiting growth and activating metabolic pathways that are beneficial to the parasite in the insect host. The post-translational modification of proteins with the Small Ubiquitin-like MOdifier (SUMO) enables dynamic regulation of cellular metabolism. SUMO can be conjugated to its targets as a monomer but can also form oligomeric chains. Here, we have investigated the role of SUMO chains in T. brucei by abolishing the ability of SUMO to polymerize. We have found that parasites able to conjugate only SUMO monomers are primed for differentiation. This was demonstrated for monomorphic lines that are normally unable to produce stumpy forms in response to quorum sensing signaling in mice, and also for pleomorphic cell lines in which stumpy cells were observed at unusually low parasitemia levels. SUMO chain mutants showed a stumpy compatible transcriptional profile and better competence to differentiate into procyclics. Our study indicates that SUMO depolymerization may represent a coordinated signal triggered during stumpy activation program.
Fil: Iribarren, Paula Ana. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Di Marzio, Lucía Ayelén. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Berazategui, Maria Agustina. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Saura, Andreu. Consejo Superior de Investigaciones Científicas; España
Fil: Coria, Mirta Lorena. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Cassataro, Juliana. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Rojas, Federico. Lancaster University; Reino Unido
Fil: Navarro, Miguel. Consejo Superior de Investigaciones Científicas; España
Fil: Alvarez, Vanina Eder. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Materia
PARASITIC DISEASE
TRYPANOSOMA BRUCEI
SUMOylation
CELL DIFFERENTIATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/267317
Acceder
id CONICETDig_2daab716fe3c81ce7ba8b52f310f0afa
oai_identifier_str oai:ri.conicet.gov.ar:11336/267317
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Depolymerization of SUMO chains induces slender to stumpy differentiation in T. brucei bloodstream parasitesIribarren, Paula AnaDi Marzio, Lucía AyelénBerazategui, Maria AgustinaSaura, AndreuCoria, Mirta LorenaCassataro, JulianaRojas, FedericoNavarro, MiguelAlvarez, Vanina EderPARASITIC DISEASETRYPANOSOMA BRUCEISUMOylationCELL DIFFERENTIATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Trypanosoma brucei are protozoan parasites that cause sleeping sickness in humans and nagana in cattle. Inside the mammalian host, a quorum sensing-like mechanism coordinates its differentiation from a slender replicative form into a quiescent stumpy form, limiting growth and activating metabolic pathways that are beneficial to the parasite in the insect host. The post-translational modification of proteins with the Small Ubiquitin-like MOdifier (SUMO) enables dynamic regulation of cellular metabolism. SUMO can be conjugated to its targets as a monomer but can also form oligomeric chains. Here, we have investigated the role of SUMO chains in T. brucei by abolishing the ability of SUMO to polymerize. We have found that parasites able to conjugate only SUMO monomers are primed for differentiation. This was demonstrated for monomorphic lines that are normally unable to produce stumpy forms in response to quorum sensing signaling in mice, and also for pleomorphic cell lines in which stumpy cells were observed at unusually low parasitemia levels. SUMO chain mutants showed a stumpy compatible transcriptional profile and better competence to differentiate into procyclics. Our study indicates that SUMO depolymerization may represent a coordinated signal triggered during stumpy activation program.Fil: Iribarren, Paula Ana. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Di Marzio, Lucía Ayelén. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Berazategui, Maria Agustina. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Saura, Andreu. Consejo Superior de Investigaciones Científicas; EspañaFil: Coria, Mirta Lorena. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Cassataro, Juliana. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Rojas, Federico. Lancaster University; Reino UnidoFil: Navarro, Miguel. Consejo Superior de Investigaciones Científicas; EspañaFil: Alvarez, Vanina Eder. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaPublic Library of Science2024-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/267317Iribarren, Paula Ana; Di Marzio, Lucía Ayelén; Berazategui, Maria Agustina; Saura, Andreu; Coria, Mirta Lorena; et al.; Depolymerization of SUMO chains induces slender to stumpy differentiation in T. brucei bloodstream parasites; Public Library of Science; PLOS Pathogens; 20; 4; 4-2024; 1-201553-7374CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1012166info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.ppat.1012166info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-23T14:53:29Zoai:ri.conicet.gov.ar:11336/267317instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-12-23 14:53:30.143CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Depolymerization of SUMO chains induces slender to stumpy differentiation in T. brucei bloodstream parasites
title Depolymerization of SUMO chains induces slender to stumpy differentiation in T. brucei bloodstream parasites
spellingShingle Depolymerization of SUMO chains induces slender to stumpy differentiation in T. brucei bloodstream parasites
Iribarren, Paula Ana
PARASITIC DISEASE
TRYPANOSOMA BRUCEI
SUMOylation
CELL DIFFERENTIATION
title_short Depolymerization of SUMO chains induces slender to stumpy differentiation in T. brucei bloodstream parasites
title_full Depolymerization of SUMO chains induces slender to stumpy differentiation in T. brucei bloodstream parasites
title_fullStr Depolymerization of SUMO chains induces slender to stumpy differentiation in T. brucei bloodstream parasites
title_full_unstemmed Depolymerization of SUMO chains induces slender to stumpy differentiation in T. brucei bloodstream parasites
title_sort Depolymerization of SUMO chains induces slender to stumpy differentiation in T. brucei bloodstream parasites
dc.creator.none.fl_str_mv Iribarren, Paula Ana
Di Marzio, Lucía Ayelén
Berazategui, Maria Agustina
Saura, Andreu
Coria, Mirta Lorena
Cassataro, Juliana
Rojas, Federico
Navarro, Miguel
Alvarez, Vanina Eder
author Iribarren, Paula Ana
author_facet Iribarren, Paula Ana
Di Marzio, Lucía Ayelén
Berazategui, Maria Agustina
Saura, Andreu
Coria, Mirta Lorena
Cassataro, Juliana
Rojas, Federico
Navarro, Miguel
Alvarez, Vanina Eder
author_role author
author2 Di Marzio, Lucía Ayelén
Berazategui, Maria Agustina
Saura, Andreu
Coria, Mirta Lorena
Cassataro, Juliana
Rojas, Federico
Navarro, Miguel
Alvarez, Vanina Eder
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PARASITIC DISEASE
TRYPANOSOMA BRUCEI
SUMOylation
CELL DIFFERENTIATION
topic PARASITIC DISEASE
TRYPANOSOMA BRUCEI
SUMOylation
CELL DIFFERENTIATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Trypanosoma brucei are protozoan parasites that cause sleeping sickness in humans and nagana in cattle. Inside the mammalian host, a quorum sensing-like mechanism coordinates its differentiation from a slender replicative form into a quiescent stumpy form, limiting growth and activating metabolic pathways that are beneficial to the parasite in the insect host. The post-translational modification of proteins with the Small Ubiquitin-like MOdifier (SUMO) enables dynamic regulation of cellular metabolism. SUMO can be conjugated to its targets as a monomer but can also form oligomeric chains. Here, we have investigated the role of SUMO chains in T. brucei by abolishing the ability of SUMO to polymerize. We have found that parasites able to conjugate only SUMO monomers are primed for differentiation. This was demonstrated for monomorphic lines that are normally unable to produce stumpy forms in response to quorum sensing signaling in mice, and also for pleomorphic cell lines in which stumpy cells were observed at unusually low parasitemia levels. SUMO chain mutants showed a stumpy compatible transcriptional profile and better competence to differentiate into procyclics. Our study indicates that SUMO depolymerization may represent a coordinated signal triggered during stumpy activation program.
Fil: Iribarren, Paula Ana. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Di Marzio, Lucía Ayelén. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Berazategui, Maria Agustina. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Saura, Andreu. Consejo Superior de Investigaciones Científicas; España
Fil: Coria, Mirta Lorena. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Cassataro, Juliana. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Rojas, Federico. Lancaster University; Reino Unido
Fil: Navarro, Miguel. Consejo Superior de Investigaciones Científicas; España
Fil: Alvarez, Vanina Eder. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
description Trypanosoma brucei are protozoan parasites that cause sleeping sickness in humans and nagana in cattle. Inside the mammalian host, a quorum sensing-like mechanism coordinates its differentiation from a slender replicative form into a quiescent stumpy form, limiting growth and activating metabolic pathways that are beneficial to the parasite in the insect host. The post-translational modification of proteins with the Small Ubiquitin-like MOdifier (SUMO) enables dynamic regulation of cellular metabolism. SUMO can be conjugated to its targets as a monomer but can also form oligomeric chains. Here, we have investigated the role of SUMO chains in T. brucei by abolishing the ability of SUMO to polymerize. We have found that parasites able to conjugate only SUMO monomers are primed for differentiation. This was demonstrated for monomorphic lines that are normally unable to produce stumpy forms in response to quorum sensing signaling in mice, and also for pleomorphic cell lines in which stumpy cells were observed at unusually low parasitemia levels. SUMO chain mutants showed a stumpy compatible transcriptional profile and better competence to differentiate into procyclics. Our study indicates that SUMO depolymerization may represent a coordinated signal triggered during stumpy activation program.
publishDate 2024
dc.date.none.fl_str_mv 2024-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/267317
Iribarren, Paula Ana; Di Marzio, Lucía Ayelén; Berazategui, Maria Agustina; Saura, Andreu; Coria, Mirta Lorena; et al.; Depolymerization of SUMO chains induces slender to stumpy differentiation in T. brucei bloodstream parasites; Public Library of Science; PLOS Pathogens; 20; 4; 4-2024; 1-20
1553-7374
CONICET Digital
CONICET
url http://hdl.handle.net/11336/267317
identifier_str_mv Iribarren, Paula Ana; Di Marzio, Lucía Ayelén; Berazategui, Maria Agustina; Saura, Andreu; Coria, Mirta Lorena; et al.; Depolymerization of SUMO chains induces slender to stumpy differentiation in T. brucei bloodstream parasites; Public Library of Science; PLOS Pathogens; 20; 4; 4-2024; 1-20
1553-7374
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1012166
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.ppat.1012166
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.952241

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