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dc.contributor.author
Ruzzi, Leonardo Rubén
dc.contributor.author
Schilman, Pablo Ernesto
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San Martín, Alvaro
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Lew, Sergio Eduardo
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Gelb, Bruce D.
dc.contributor.author
Pagani, Mario Rafael
dc.date.available
2021-09-17T12:41:41Z
dc.date.issued
2020-05
dc.identifier.citation
Ruzzi, Leonardo Rubén; Schilman, Pablo Ernesto; San Martín, Alvaro; Lew, Sergio Eduardo; Gelb, Bruce D.; et al.; The Phosphatase CSW Controls Life Span by Insulin Signaling and Metabolism Throughout Adult Life in Drosophila; Frontiers Media S.A.; Frontiers in Genetics; 11; 5-2020; 1-15
dc.identifier.issn
1664-8021
dc.identifier.uri
http://hdl.handle.net/11336/140644
dc.description.abstract
Noonan syndrome and related disorders are caused by mutations in genes encoding for proteins of the RAS-ERK1/2 signaling pathway, which affect development by enhanced ERK1/2 activity. However, the mutations’ effects throughout adult life are unclear. In this study, we identify that the protein most commonly affected in Noonan syndrome, the phosphatase SHP2, known in Drosophila as corkscrew (CSW), controls life span, triglyceride levels, and metabolism without affecting ERK signaling pathway. We found that CSW loss-of-function mutations extended life span by interacting with components of the insulin signaling pathway and impairing AKT activity in adult flies. By expressing csw-RNAi in different organs, we determined that CSW extended life span by acting in organs that regulate energy availability, including gut, fat body and neurons. In contrast to that in control animals, loss of CSW leads to reduced homeostasis in metabolic rate during activity. Clinically relevant gain-of-function csw allele reduced life span, when expressed in fat body, but not in other tissues. However, overexpression of a wild-type allele did not affect life span, showing a specific effect of the gain-of-function allele independently of a gene dosage effect. We concluded that CSW normally regulates life span and that mutations in SHP2 are expected to have critical effects throughout life by insulin-dependent mechanisms in addition to the well-known RAS-ERK1/2-dependent developmental alterations.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Frontiers Media S.A.
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
CSW LOSS AND GAIN-OF-FUNCTION MUTATIONS
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DROSOPHILA
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INSULIN SIGNALING
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LIFE SPAN
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METABOLISM
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Otros Tópicos Biológicos
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
The Phosphatase CSW Controls Life Span by Insulin Signaling and Metabolism Throughout Adult Life in Drosophila
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2021-09-07T18:57:09Z
dc.journal.volume
11
dc.journal.pagination
1-15
dc.journal.pais
Suiza
dc.journal.ciudad
Lausanne
dc.description.fil
Fil: Ruzzi, Leonardo Rubén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
dc.description.fil
Fil: Schilman, Pablo Ernesto. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: San Martín, Alvaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
dc.description.fil
Fil: Lew, Sergio Eduardo. Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Ingeniería Biomédica; Argentina
dc.description.fil
Fil: Gelb, Bruce D.. Icahn School of Medicine at Mount Sinai; Estados Unidos
dc.description.fil
Fil: Pagani, Mario Rafael. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
dc.journal.title
Frontiers in Genetics
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fgene.2020.00364/full
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3389/fgene.2020.00364
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