Mice deficient in ribosomal protein S6 phosphorylation suffer from muscle weakness that reflects a growth defect and energy deficit

Autores
Ruvinsky, Igor; Katz, Maximiliano Javier; Dreazen, Avigail; Gielchinsky, Yuval; Saada, Ann; Freedman, Nanette; Mishani, Eyal; Zimmerman, Gabriel; Kasir, Judith; Meyuhas, Oded
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
BACKGROUND: Mice, whose ribosomal protein S6 cannot be phosphorylated due to replacement of all five phosphorylatable serine residues by alanines (rpS6(P-/-)), are viable and fertile. However, phenotypic characterization of these mice and embryo fibroblasts derived from them, has established the role of these modifications in the regulation of the size of several cell types, as well as pancreatic beta-cell function and glucose homeostasis. A relatively passive behavior of these mice has raised the possibility that they suffer from muscle weakness, which has, indeed, been confirmed by a variety of physical performance tests. METHODOLOGY/PRINCIPAL FINDINGS: A large variety of experimental methodologies, including morphometric measurements of histological preparations, high throughput proteomic analysis, positron emission tomography (PET) and numerous biochemical assays, were used in an attempt to establish the mechanism underlying the relative weakness of rpS6(P-/-) muscles. Collectively, these experiments have demonstrated that the physical inferiority appears to result from two defects: a) a decrease in total muscle mass that reflects impaired growth, rather than aberrant differentiation of myofibers, as well as a diminished abundance of contractile proteins; and b) a reduced content of ATP and phosphocreatine, two readily available energy sources. The abundance of three mitochondrial proteins has been shown to diminish in the knockin mouse. However, the apparent energy deficiency in this genotype does not result from a lower mitochondrial mass or compromised activity of enzymes of the oxidative phosphorylation, nor does it reflect a decline in insulin-dependent glucose uptake, or diminution in storage of glycogen or triacylglycerol (TG) in the muscle. CONCLUSIONS/SIGNIFICANCE: This study establishes rpS6 phosphorylation as a determinant of muscle strength through its role in regulation of myofiber growth and energy content. Interestingly, a similar role has been assigned for ribosomal protein S6 kinase 1, even though it regulates myoblast growth in an rpS6 phosphorylation-independent fashion.
Fil: Ruvinsky, Igor. The Hebrew University Of Jerusalem; Israel
Fil: Katz, Maximiliano Javier. The Hebrew University Of Jerusalem; Israel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Dreazen, Avigail. The Hebrew University Of Jerusalem; Israel
Fil: Gielchinsky, Yuval. Hadassah Medical Center; Israel
Fil: Saada, Ann. Hadassah Medical Center; Israel
Fil: Freedman, Nanette. Hadassah Medical Center; Israel
Fil: Mishani, Eyal. Hadassah Medical Center; Israel
Fil: Zimmerman, Gabriel. The Hebrew University Of Jerusalem; Israel
Fil: Kasir, Judith. The Hebrew University Of Jerusalem; Israel
Fil: Meyuhas, Oded. The Hebrew University Of Jerusalem; Israel
Materia
MUSCLE WEAKNESS
GLUCOSE HOMEOSTASIS
RIBOSOMAL PROTEIN S6
MYOBLAST
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/20753

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network_name_str CONICET Digital (CONICET)
spelling Mice deficient in ribosomal protein S6 phosphorylation suffer from muscle weakness that reflects a growth defect and energy deficitRuvinsky, IgorKatz, Maximiliano JavierDreazen, AvigailGielchinsky, YuvalSaada, AnnFreedman, NanetteMishani, EyalZimmerman, GabrielKasir, JudithMeyuhas, OdedMUSCLE WEAKNESSGLUCOSE HOMEOSTASISRIBOSOMAL PROTEIN S6MYOBLASThttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1BACKGROUND: Mice, whose ribosomal protein S6 cannot be phosphorylated due to replacement of all five phosphorylatable serine residues by alanines (rpS6(P-/-)), are viable and fertile. However, phenotypic characterization of these mice and embryo fibroblasts derived from them, has established the role of these modifications in the regulation of the size of several cell types, as well as pancreatic beta-cell function and glucose homeostasis. A relatively passive behavior of these mice has raised the possibility that they suffer from muscle weakness, which has, indeed, been confirmed by a variety of physical performance tests. METHODOLOGY/PRINCIPAL FINDINGS: A large variety of experimental methodologies, including morphometric measurements of histological preparations, high throughput proteomic analysis, positron emission tomography (PET) and numerous biochemical assays, were used in an attempt to establish the mechanism underlying the relative weakness of rpS6(P-/-) muscles. Collectively, these experiments have demonstrated that the physical inferiority appears to result from two defects: a) a decrease in total muscle mass that reflects impaired growth, rather than aberrant differentiation of myofibers, as well as a diminished abundance of contractile proteins; and b) a reduced content of ATP and phosphocreatine, two readily available energy sources. The abundance of three mitochondrial proteins has been shown to diminish in the knockin mouse. However, the apparent energy deficiency in this genotype does not result from a lower mitochondrial mass or compromised activity of enzymes of the oxidative phosphorylation, nor does it reflect a decline in insulin-dependent glucose uptake, or diminution in storage of glycogen or triacylglycerol (TG) in the muscle. CONCLUSIONS/SIGNIFICANCE: This study establishes rpS6 phosphorylation as a determinant of muscle strength through its role in regulation of myofiber growth and energy content. Interestingly, a similar role has been assigned for ribosomal protein S6 kinase 1, even though it regulates myoblast growth in an rpS6 phosphorylation-independent fashion.Fil: Ruvinsky, Igor. The Hebrew University Of Jerusalem; IsraelFil: Katz, Maximiliano Javier. The Hebrew University Of Jerusalem; Israel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Dreazen, Avigail. The Hebrew University Of Jerusalem; IsraelFil: Gielchinsky, Yuval. Hadassah Medical Center; IsraelFil: Saada, Ann. Hadassah Medical Center; IsraelFil: Freedman, Nanette. Hadassah Medical Center; IsraelFil: Mishani, Eyal. Hadassah Medical Center; IsraelFil: Zimmerman, Gabriel. The Hebrew University Of Jerusalem; IsraelFil: Kasir, Judith. The Hebrew University Of Jerusalem; IsraelFil: Meyuhas, Oded. The Hebrew University Of Jerusalem; IsraelPublic Library of Science2009-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/20753Ruvinsky, Igor; Katz, Maximiliano Javier; Dreazen, Avigail; Gielchinsky, Yuval; Saada, Ann; et al.; Mice deficient in ribosomal protein S6 phosphorylation suffer from muscle weakness that reflects a growth defect and energy deficit; Public Library of Science; Plos One; 4; 5; 5-2009; e56181932-62031932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0005618info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0005618info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:55:57Zoai:ri.conicet.gov.ar:11336/20753instacron: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 09:55:57.551CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mice deficient in ribosomal protein S6 phosphorylation suffer from muscle weakness that reflects a growth defect and energy deficit
title Mice deficient in ribosomal protein S6 phosphorylation suffer from muscle weakness that reflects a growth defect and energy deficit
spellingShingle Mice deficient in ribosomal protein S6 phosphorylation suffer from muscle weakness that reflects a growth defect and energy deficit
Ruvinsky, Igor
MUSCLE WEAKNESS
GLUCOSE HOMEOSTASIS
RIBOSOMAL PROTEIN S6
MYOBLAST
title_short Mice deficient in ribosomal protein S6 phosphorylation suffer from muscle weakness that reflects a growth defect and energy deficit
title_full Mice deficient in ribosomal protein S6 phosphorylation suffer from muscle weakness that reflects a growth defect and energy deficit
title_fullStr Mice deficient in ribosomal protein S6 phosphorylation suffer from muscle weakness that reflects a growth defect and energy deficit
title_full_unstemmed Mice deficient in ribosomal protein S6 phosphorylation suffer from muscle weakness that reflects a growth defect and energy deficit
title_sort Mice deficient in ribosomal protein S6 phosphorylation suffer from muscle weakness that reflects a growth defect and energy deficit
dc.creator.none.fl_str_mv Ruvinsky, Igor
Katz, Maximiliano Javier
Dreazen, Avigail
Gielchinsky, Yuval
Saada, Ann
Freedman, Nanette
Mishani, Eyal
Zimmerman, Gabriel
Kasir, Judith
Meyuhas, Oded
author Ruvinsky, Igor
author_facet Ruvinsky, Igor
Katz, Maximiliano Javier
Dreazen, Avigail
Gielchinsky, Yuval
Saada, Ann
Freedman, Nanette
Mishani, Eyal
Zimmerman, Gabriel
Kasir, Judith
Meyuhas, Oded
author_role author
author2 Katz, Maximiliano Javier
Dreazen, Avigail
Gielchinsky, Yuval
Saada, Ann
Freedman, Nanette
Mishani, Eyal
Zimmerman, Gabriel
Kasir, Judith
Meyuhas, Oded
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv MUSCLE WEAKNESS
GLUCOSE HOMEOSTASIS
RIBOSOMAL PROTEIN S6
MYOBLAST
topic MUSCLE WEAKNESS
GLUCOSE HOMEOSTASIS
RIBOSOMAL PROTEIN S6
MYOBLAST
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv BACKGROUND: Mice, whose ribosomal protein S6 cannot be phosphorylated due to replacement of all five phosphorylatable serine residues by alanines (rpS6(P-/-)), are viable and fertile. However, phenotypic characterization of these mice and embryo fibroblasts derived from them, has established the role of these modifications in the regulation of the size of several cell types, as well as pancreatic beta-cell function and glucose homeostasis. A relatively passive behavior of these mice has raised the possibility that they suffer from muscle weakness, which has, indeed, been confirmed by a variety of physical performance tests. METHODOLOGY/PRINCIPAL FINDINGS: A large variety of experimental methodologies, including morphometric measurements of histological preparations, high throughput proteomic analysis, positron emission tomography (PET) and numerous biochemical assays, were used in an attempt to establish the mechanism underlying the relative weakness of rpS6(P-/-) muscles. Collectively, these experiments have demonstrated that the physical inferiority appears to result from two defects: a) a decrease in total muscle mass that reflects impaired growth, rather than aberrant differentiation of myofibers, as well as a diminished abundance of contractile proteins; and b) a reduced content of ATP and phosphocreatine, two readily available energy sources. The abundance of three mitochondrial proteins has been shown to diminish in the knockin mouse. However, the apparent energy deficiency in this genotype does not result from a lower mitochondrial mass or compromised activity of enzymes of the oxidative phosphorylation, nor does it reflect a decline in insulin-dependent glucose uptake, or diminution in storage of glycogen or triacylglycerol (TG) in the muscle. CONCLUSIONS/SIGNIFICANCE: This study establishes rpS6 phosphorylation as a determinant of muscle strength through its role in regulation of myofiber growth and energy content. Interestingly, a similar role has been assigned for ribosomal protein S6 kinase 1, even though it regulates myoblast growth in an rpS6 phosphorylation-independent fashion.
Fil: Ruvinsky, Igor. The Hebrew University Of Jerusalem; Israel
Fil: Katz, Maximiliano Javier. The Hebrew University Of Jerusalem; Israel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Dreazen, Avigail. The Hebrew University Of Jerusalem; Israel
Fil: Gielchinsky, Yuval. Hadassah Medical Center; Israel
Fil: Saada, Ann. Hadassah Medical Center; Israel
Fil: Freedman, Nanette. Hadassah Medical Center; Israel
Fil: Mishani, Eyal. Hadassah Medical Center; Israel
Fil: Zimmerman, Gabriel. The Hebrew University Of Jerusalem; Israel
Fil: Kasir, Judith. The Hebrew University Of Jerusalem; Israel
Fil: Meyuhas, Oded. The Hebrew University Of Jerusalem; Israel
description BACKGROUND: Mice, whose ribosomal protein S6 cannot be phosphorylated due to replacement of all five phosphorylatable serine residues by alanines (rpS6(P-/-)), are viable and fertile. However, phenotypic characterization of these mice and embryo fibroblasts derived from them, has established the role of these modifications in the regulation of the size of several cell types, as well as pancreatic beta-cell function and glucose homeostasis. A relatively passive behavior of these mice has raised the possibility that they suffer from muscle weakness, which has, indeed, been confirmed by a variety of physical performance tests. METHODOLOGY/PRINCIPAL FINDINGS: A large variety of experimental methodologies, including morphometric measurements of histological preparations, high throughput proteomic analysis, positron emission tomography (PET) and numerous biochemical assays, were used in an attempt to establish the mechanism underlying the relative weakness of rpS6(P-/-) muscles. Collectively, these experiments have demonstrated that the physical inferiority appears to result from two defects: a) a decrease in total muscle mass that reflects impaired growth, rather than aberrant differentiation of myofibers, as well as a diminished abundance of contractile proteins; and b) a reduced content of ATP and phosphocreatine, two readily available energy sources. The abundance of three mitochondrial proteins has been shown to diminish in the knockin mouse. However, the apparent energy deficiency in this genotype does not result from a lower mitochondrial mass or compromised activity of enzymes of the oxidative phosphorylation, nor does it reflect a decline in insulin-dependent glucose uptake, or diminution in storage of glycogen or triacylglycerol (TG) in the muscle. CONCLUSIONS/SIGNIFICANCE: This study establishes rpS6 phosphorylation as a determinant of muscle strength through its role in regulation of myofiber growth and energy content. Interestingly, a similar role has been assigned for ribosomal protein S6 kinase 1, even though it regulates myoblast growth in an rpS6 phosphorylation-independent fashion.
publishDate 2009
dc.date.none.fl_str_mv 2009-05
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/11336/20753
Ruvinsky, Igor; Katz, Maximiliano Javier; Dreazen, Avigail; Gielchinsky, Yuval; Saada, Ann; et al.; Mice deficient in ribosomal protein S6 phosphorylation suffer from muscle weakness that reflects a growth defect and energy deficit; Public Library of Science; Plos One; 4; 5; 5-2009; e5618
1932-6203
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/20753
identifier_str_mv Ruvinsky, Igor; Katz, Maximiliano Javier; Dreazen, Avigail; Gielchinsky, Yuval; Saada, Ann; et al.; Mice deficient in ribosomal protein S6 phosphorylation suffer from muscle weakness that reflects a growth defect and energy deficit; Public Library of Science; Plos One; 4; 5; 5-2009; e5618
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0005618
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0005618
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
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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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