Purine homeostasis is necessary for developmental timing, germline maintenance and muscle integrity in caenorhabditis elegans

Purine homeostasis is ensured through a metabolic network widely conserved from prokaryotes to humans. Purines can either be synthesized de novo, reused, or produced by interconversion of extant metabolites using the so-called recycling pathway. Although thoroughly characterized in microorganisms, s...

ver descrição completa

Detalhes bibliográficos
Autores: Marsac, Roxane, Pinson, Benoît, Saint-Marc, Christelle, Olmedo López, María, Artal Sanz, Marta, Daignan-Fornier, Bertrand, Gomes, José Eduardo
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Recursos:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/133349
Acesso em linha:https://hdl.handle.net/11441/133349
https://doi.org/10.1534/genetics.118.301062
Access Level:acceso abierto
Palavra-chave:ADSL deficiency
AICAR
Metabolism
Purine salvage pathway
SAICAR
SZMP
ZMP
id ES_f1410db8e025ef11dfd22e212a8c99db
oai_identifier_str oai:idus.us.es:11441/133349
network_acronym_str ES
network_name_str España
repository_id_str
spelling Purine homeostasis is necessary for developmental timing, germline maintenance and muscle integrity in caenorhabditis elegansMarsac, RoxanePinson, BenoîtSaint-Marc, ChristelleOlmedo López, MaríaArtal Sanz, MartaDaignan-Fornier, BertrandGomes, José EduardoADSL deficiencyAICARMetabolismPurine salvage pathwaySAICARSZMPZMPPurine homeostasis is ensured through a metabolic network widely conserved from prokaryotes to humans. Purines can either be synthesized de novo, reused, or produced by interconversion of extant metabolites using the so-called recycling pathway. Although thoroughly characterized in microorganisms, such as yeast or bacteria, little is known about regulation of the purine biosynthesis network in metazoans. In humans, several diseases are linked to purine metabolism through as yet poorly understood etiologies. Particularly, the deficiency in adenylosuccinate lyase (ADSL)-an enzyme involved both in the purine de novo and recycling pathways-causes severe muscular and neuronal symptoms. In order to address the mechanisms underlying this deficiency, we established Caenorhabditis elegans as a metazoan model organism to study purine metabolism, while focusing on ADSL. We show that the purine biosynthesis network is functionally conserved in C. elegans. Moreover, adsl-1 (the gene encoding ADSL in C. elegans) is required for developmental timing, germline stem cell maintenance and muscle integrity. Importantly, these traits are not affected when solely the de novo pathway is abolished, and we present evidence that germline maintenance is linked specifically to ADSL activity in the recycling pathway. Hence, our results allow developmental and tissue specific phenotypes to be ascribed to separable steps of the purine metabolic network in an animal model.National Institutes of Health (NIH) P40 OD010440, U41 HG002223Ministerio de Economía y Competitividad RYC-2010-06167, RYC2014-15551Genetics Society of AmericaGenéticaNational Institutes of Health (NIH)Ministerio de Economía y Competitividad (MINECO). España2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/133349https://doi.org/10.1534/genetics.118.301062reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésGenetics, 211 (4), 1297-1313.P40 OD010440U41 HG002223RYC-2010-06167RYC2014-15551https://doi.org/10.1534/genetics.118.301062info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1333492026-06-17T12:51:07Z
dc.title.none.fl_str_mv Purine homeostasis is necessary for developmental timing, germline maintenance and muscle integrity in caenorhabditis elegans
title Purine homeostasis is necessary for developmental timing, germline maintenance and muscle integrity in caenorhabditis elegans
spellingShingle Purine homeostasis is necessary for developmental timing, germline maintenance and muscle integrity in caenorhabditis elegans
Marsac, Roxane
ADSL deficiency
AICAR
Metabolism
Purine salvage pathway
SAICAR
SZMP
ZMP
title_short Purine homeostasis is necessary for developmental timing, germline maintenance and muscle integrity in caenorhabditis elegans
title_full Purine homeostasis is necessary for developmental timing, germline maintenance and muscle integrity in caenorhabditis elegans
title_fullStr Purine homeostasis is necessary for developmental timing, germline maintenance and muscle integrity in caenorhabditis elegans
title_full_unstemmed Purine homeostasis is necessary for developmental timing, germline maintenance and muscle integrity in caenorhabditis elegans
title_sort Purine homeostasis is necessary for developmental timing, germline maintenance and muscle integrity in caenorhabditis elegans
dc.creator.none.fl_str_mv Marsac, Roxane
Pinson, Benoît
Saint-Marc, Christelle
Olmedo López, María
Artal Sanz, Marta
Daignan-Fornier, Bertrand
Gomes, José Eduardo
author Marsac, Roxane
author_facet Marsac, Roxane
Pinson, Benoît
Saint-Marc, Christelle
Olmedo López, María
Artal Sanz, Marta
Daignan-Fornier, Bertrand
Gomes, José Eduardo
author_role author
author2 Pinson, Benoît
Saint-Marc, Christelle
Olmedo López, María
Artal Sanz, Marta
Daignan-Fornier, Bertrand
Gomes, José Eduardo
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Genética
National Institutes of Health (NIH)
Ministerio de Economía y Competitividad (MINECO). España
dc.subject.none.fl_str_mv ADSL deficiency
AICAR
Metabolism
Purine salvage pathway
SAICAR
SZMP
ZMP
topic ADSL deficiency
AICAR
Metabolism
Purine salvage pathway
SAICAR
SZMP
ZMP
description Purine homeostasis is ensured through a metabolic network widely conserved from prokaryotes to humans. Purines can either be synthesized de novo, reused, or produced by interconversion of extant metabolites using the so-called recycling pathway. Although thoroughly characterized in microorganisms, such as yeast or bacteria, little is known about regulation of the purine biosynthesis network in metazoans. In humans, several diseases are linked to purine metabolism through as yet poorly understood etiologies. Particularly, the deficiency in adenylosuccinate lyase (ADSL)-an enzyme involved both in the purine de novo and recycling pathways-causes severe muscular and neuronal symptoms. In order to address the mechanisms underlying this deficiency, we established Caenorhabditis elegans as a metazoan model organism to study purine metabolism, while focusing on ADSL. We show that the purine biosynthesis network is functionally conserved in C. elegans. Moreover, adsl-1 (the gene encoding ADSL in C. elegans) is required for developmental timing, germline stem cell maintenance and muscle integrity. Importantly, these traits are not affected when solely the de novo pathway is abolished, and we present evidence that germline maintenance is linked specifically to ADSL activity in the recycling pathway. Hence, our results allow developmental and tissue specific phenotypes to be ascribed to separable steps of the purine metabolic network in an animal model.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/133349
https://doi.org/10.1534/genetics.118.301062
url https://hdl.handle.net/11441/133349
https://doi.org/10.1534/genetics.118.301062
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Genetics, 211 (4), 1297-1313.
P40 OD010440
U41 HG002223
RYC-2010-06167
RYC2014-15551
https://doi.org/10.1534/genetics.118.301062
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Genetics Society of America
publisher.none.fl_str_mv Genetics Society of America
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869424111989555200
score 15,300719

Registos relacionados