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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/20753
Ver los metadatos del registro completo
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oai:ri.conicet.gov.ar:11336/20753 |
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3498 |
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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/ |
dc.format.none.fl_str_mv |
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) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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1844613683903201280 |
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13.070432 |