An AMP-activated protein kinase complex with two distinctive alpha subunits is involved in nutritional stress responses in Trypanosoma cruzi
- Autores
- Sternlieb, Tamara; Schoijet, Alejandra Cecilia; Genta, Patricio D.; Vilchez Larrea, Salomé Catalina; Alonso, Guillermo Daniel
- Año de publicación
- 2021
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Trypanosoma cruzi, the etiological agent of Chagas disease, has a digenetic life cycle. In itspassage from the insect vector to the mammalian host, and vice versa, it must be preparedto cope with abrupt changes in environmental conditions, such as carbon source, pH, temperatureand osmolarity, in order to survive. Sensing and signaling pathways that allow theparasite to adapt, have unique characteristics with respect to their hosts and other free-livingorganisms. Many of the canonical proteins involved in these transduction pathways havenot yet been found in the genomes of these parasites because they present divergenceseither at the functional, structural and/or protein sequence level. All of this makes thesepathways promising targets for therapeutic drugs. The AMP-activated protein kinase(AMPK) is a serine/threonine kinase activated by environmental stresses such as osmoticstress, hypoxia, ischaemia and exercise that results in reduction of ATP and increase ofAMP levels. Thus, AMPK is regarded as a fuel gauge, functioning both as a nutrient and anenergy sensor, to maintain energy homeostasis and, eventually, to protect cells from deathby nutrient starvation. In the present study we report the characterization of AMPK complexesfor the first time in T. cruzi and propose the function of TcAMPK as a novel regulatorof nutritional stress in epimastigote forms. We show that there is phosphotransferase activityspecific for SAMS peptide in epimastigotes extracts, which is inhibited by Compound C andis modulated by carbon source availability. In addition, TcAMPKα2 subunit has an unprecedentedfunctional substitution (Ser x Thr) at the activation loop and its overexpression in epimastigotesled to higher autophagic activity during prolonged nutritional stress. Moreover,the over-expression of the catalytic subunits resulted in antagonistic phenotypes associatedwith proliferation. Together, these results point to a role of TcAMPK in autophagy and nutrient sensing, key processes for the survival of trypanosomatids and for its life cycleprogression.
Fil: Sternlieb, Tamara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Schoijet, Alejandra Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Genta, Patricio D.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Vilchez Larrea, Salomé Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Alonso, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina - Materia
-
Trypanosoma cruzi
AMPK
Phosphorylation
Autophagy - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/138059
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CONICET Digital (CONICET) |
spelling |
An AMP-activated protein kinase complex with two distinctive alpha subunits is involved in nutritional stress responses in Trypanosoma cruziSternlieb, TamaraSchoijet, Alejandra CeciliaGenta, Patricio D.Vilchez Larrea, Salomé CatalinaAlonso, Guillermo DanielTrypanosoma cruziAMPKPhosphorylationAutophagyhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Trypanosoma cruzi, the etiological agent of Chagas disease, has a digenetic life cycle. In itspassage from the insect vector to the mammalian host, and vice versa, it must be preparedto cope with abrupt changes in environmental conditions, such as carbon source, pH, temperatureand osmolarity, in order to survive. Sensing and signaling pathways that allow theparasite to adapt, have unique characteristics with respect to their hosts and other free-livingorganisms. Many of the canonical proteins involved in these transduction pathways havenot yet been found in the genomes of these parasites because they present divergenceseither at the functional, structural and/or protein sequence level. All of this makes thesepathways promising targets for therapeutic drugs. The AMP-activated protein kinase(AMPK) is a serine/threonine kinase activated by environmental stresses such as osmoticstress, hypoxia, ischaemia and exercise that results in reduction of ATP and increase ofAMP levels. Thus, AMPK is regarded as a fuel gauge, functioning both as a nutrient and anenergy sensor, to maintain energy homeostasis and, eventually, to protect cells from deathby nutrient starvation. In the present study we report the characterization of AMPK complexesfor the first time in T. cruzi and propose the function of TcAMPK as a novel regulatorof nutritional stress in epimastigote forms. We show that there is phosphotransferase activityspecific for SAMS peptide in epimastigotes extracts, which is inhibited by Compound C andis modulated by carbon source availability. In addition, TcAMPKα2 subunit has an unprecedentedfunctional substitution (Ser x Thr) at the activation loop and its overexpression in epimastigotesled to higher autophagic activity during prolonged nutritional stress. Moreover,the over-expression of the catalytic subunits resulted in antagonistic phenotypes associatedwith proliferation. Together, these results point to a role of TcAMPK in autophagy and nutrient sensing, key processes for the survival of trypanosomatids and for its life cycleprogression.Fil: Sternlieb, Tamara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Schoijet, Alejandra Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Genta, Patricio D.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Vilchez Larrea, Salomé Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Alonso, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaPublic Library of Science2021-05-24info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/138059Sternlieb, Tamara; Schoijet, Alejandra Cecilia; Genta, Patricio D.; Vilchez Larrea, Salomé Catalina; Alonso, Guillermo Daniel; An AMP-activated protein kinase complex with two distinctive alpha subunits is involved in nutritional stress responses in Trypanosoma cruzi; Public Library of Science; Plos Neglected Tropical Diseases; 15; 5; 24-5-2021; 1-221935-2735CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://dx.plos.org/10.1371/journal.pntd.0009435info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pntd.0009435info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:33:00Zoai:ri.conicet.gov.ar:11336/138059instacron: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:34982025-09-29 09:33:00.803CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
An AMP-activated protein kinase complex with two distinctive alpha subunits is involved in nutritional stress responses in Trypanosoma cruzi |
title |
An AMP-activated protein kinase complex with two distinctive alpha subunits is involved in nutritional stress responses in Trypanosoma cruzi |
spellingShingle |
An AMP-activated protein kinase complex with two distinctive alpha subunits is involved in nutritional stress responses in Trypanosoma cruzi Sternlieb, Tamara Trypanosoma cruzi AMPK Phosphorylation Autophagy |
title_short |
An AMP-activated protein kinase complex with two distinctive alpha subunits is involved in nutritional stress responses in Trypanosoma cruzi |
title_full |
An AMP-activated protein kinase complex with two distinctive alpha subunits is involved in nutritional stress responses in Trypanosoma cruzi |
title_fullStr |
An AMP-activated protein kinase complex with two distinctive alpha subunits is involved in nutritional stress responses in Trypanosoma cruzi |
title_full_unstemmed |
An AMP-activated protein kinase complex with two distinctive alpha subunits is involved in nutritional stress responses in Trypanosoma cruzi |
title_sort |
An AMP-activated protein kinase complex with two distinctive alpha subunits is involved in nutritional stress responses in Trypanosoma cruzi |
dc.creator.none.fl_str_mv |
Sternlieb, Tamara Schoijet, Alejandra Cecilia Genta, Patricio D. Vilchez Larrea, Salomé Catalina Alonso, Guillermo Daniel |
author |
Sternlieb, Tamara |
author_facet |
Sternlieb, Tamara Schoijet, Alejandra Cecilia Genta, Patricio D. Vilchez Larrea, Salomé Catalina Alonso, Guillermo Daniel |
author_role |
author |
author2 |
Schoijet, Alejandra Cecilia Genta, Patricio D. Vilchez Larrea, Salomé Catalina Alonso, Guillermo Daniel |
author2_role |
author author author author |
dc.subject.none.fl_str_mv |
Trypanosoma cruzi AMPK Phosphorylation Autophagy |
topic |
Trypanosoma cruzi AMPK Phosphorylation Autophagy |
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 cruzi, the etiological agent of Chagas disease, has a digenetic life cycle. In itspassage from the insect vector to the mammalian host, and vice versa, it must be preparedto cope with abrupt changes in environmental conditions, such as carbon source, pH, temperatureand osmolarity, in order to survive. Sensing and signaling pathways that allow theparasite to adapt, have unique characteristics with respect to their hosts and other free-livingorganisms. Many of the canonical proteins involved in these transduction pathways havenot yet been found in the genomes of these parasites because they present divergenceseither at the functional, structural and/or protein sequence level. All of this makes thesepathways promising targets for therapeutic drugs. The AMP-activated protein kinase(AMPK) is a serine/threonine kinase activated by environmental stresses such as osmoticstress, hypoxia, ischaemia and exercise that results in reduction of ATP and increase ofAMP levels. Thus, AMPK is regarded as a fuel gauge, functioning both as a nutrient and anenergy sensor, to maintain energy homeostasis and, eventually, to protect cells from deathby nutrient starvation. In the present study we report the characterization of AMPK complexesfor the first time in T. cruzi and propose the function of TcAMPK as a novel regulatorof nutritional stress in epimastigote forms. We show that there is phosphotransferase activityspecific for SAMS peptide in epimastigotes extracts, which is inhibited by Compound C andis modulated by carbon source availability. In addition, TcAMPKα2 subunit has an unprecedentedfunctional substitution (Ser x Thr) at the activation loop and its overexpression in epimastigotesled to higher autophagic activity during prolonged nutritional stress. Moreover,the over-expression of the catalytic subunits resulted in antagonistic phenotypes associatedwith proliferation. Together, these results point to a role of TcAMPK in autophagy and nutrient sensing, key processes for the survival of trypanosomatids and for its life cycleprogression. Fil: Sternlieb, Tamara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Schoijet, Alejandra Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Genta, Patricio D.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Vilchez Larrea, Salomé Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Alonso, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina |
description |
Trypanosoma cruzi, the etiological agent of Chagas disease, has a digenetic life cycle. In itspassage from the insect vector to the mammalian host, and vice versa, it must be preparedto cope with abrupt changes in environmental conditions, such as carbon source, pH, temperatureand osmolarity, in order to survive. Sensing and signaling pathways that allow theparasite to adapt, have unique characteristics with respect to their hosts and other free-livingorganisms. Many of the canonical proteins involved in these transduction pathways havenot yet been found in the genomes of these parasites because they present divergenceseither at the functional, structural and/or protein sequence level. All of this makes thesepathways promising targets for therapeutic drugs. The AMP-activated protein kinase(AMPK) is a serine/threonine kinase activated by environmental stresses such as osmoticstress, hypoxia, ischaemia and exercise that results in reduction of ATP and increase ofAMP levels. Thus, AMPK is regarded as a fuel gauge, functioning both as a nutrient and anenergy sensor, to maintain energy homeostasis and, eventually, to protect cells from deathby nutrient starvation. In the present study we report the characterization of AMPK complexesfor the first time in T. cruzi and propose the function of TcAMPK as a novel regulatorof nutritional stress in epimastigote forms. We show that there is phosphotransferase activityspecific for SAMS peptide in epimastigotes extracts, which is inhibited by Compound C andis modulated by carbon source availability. In addition, TcAMPKα2 subunit has an unprecedentedfunctional substitution (Ser x Thr) at the activation loop and its overexpression in epimastigotesled to higher autophagic activity during prolonged nutritional stress. Moreover,the over-expression of the catalytic subunits resulted in antagonistic phenotypes associatedwith proliferation. Together, these results point to a role of TcAMPK in autophagy and nutrient sensing, key processes for the survival of trypanosomatids and for its life cycleprogression. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-05-24 |
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/11336/138059 Sternlieb, Tamara; Schoijet, Alejandra Cecilia; Genta, Patricio D.; Vilchez Larrea, Salomé Catalina; Alonso, Guillermo Daniel; An AMP-activated protein kinase complex with two distinctive alpha subunits is involved in nutritional stress responses in Trypanosoma cruzi; Public Library of Science; Plos Neglected Tropical Diseases; 15; 5; 24-5-2021; 1-22 1935-2735 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/138059 |
identifier_str_mv |
Sternlieb, Tamara; Schoijet, Alejandra Cecilia; Genta, Patricio D.; Vilchez Larrea, Salomé Catalina; Alonso, Guillermo Daniel; An AMP-activated protein kinase complex with two distinctive alpha subunits is involved in nutritional stress responses in Trypanosoma cruzi; Public Library of Science; Plos Neglected Tropical Diseases; 15; 5; 24-5-2021; 1-22 1935-2735 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://dx.plos.org/10.1371/journal.pntd.0009435 info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pntd.0009435 |
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 |
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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1844613010414370816 |
score |
13.070432 |