A novel short splice variant of the tumour suppressor LKB1 is required for spermiogenesis

Autores
Towler, Mhairi C.; Fogarty, Sarah; Hawley, Simon A.; Pan, David A.; Martin, David M. A.; Morrice, Nicolas A.; McCarthy, Afshan; Galardo, Maria Noel Lujan; Meroni, Silvina Beatriz; Cigorraga, Selva Beatriz; Ashworth, Alan; Sakamoto, Kei; Hardie, D. Grahame
Año de publicación
2008
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
LKB1 was discovered as a tumour suppressor mutated in Peutz-Jeghers syndrome, and is a gene involved in cell polarity as well as an upstream protein kinase for members of the AMP-activated protein kinase family. We report that mammals express two splice variants caused by alternate usage of 3′-exons. LKB1L is the previously described form, while LKB1s is a novel form in which the last 63 residues are replaced by a unique 39-residue sequence lacking known phosphorylation (Ser431) and farnesylation (Cys433) sites. Both isoforms are widely expressed in rodent and human tissues, although LKB1s is particularly abundant in haploid spermatids in the testis. Male mice in which expression of Lkb1s is knocked out are sterile, with the number of mature spermatozoa in the epididymis being dramatically reduced, and those spermatozoa that are produced have heads with an abnormal morphology and are non-motile. These results identify a previously undetected variant of LKB1, and suggest that it has a crucial role in spermiogenesis and male fertility.
Fil: Towler, Mhairi C.. University Of Dundee; Reino Unido
Fil: Fogarty, Sarah. University Of Dundee; Reino Unido
Fil: Hawley, Simon A.. University Of Dundee; Reino Unido
Fil: Pan, David A.. University Of Dundee; Reino Unido
Fil: Martin, David M. A.. University Of Dundee; Reino Unido
Fil: Morrice, Nicolas A.. University Of Dundee; Reino Unido
Fil: McCarthy, Afshan. The Institute Of Cancer Research; Reino Unido
Fil: Galardo, Maria Noel Lujan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Meroni, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Cigorraga, Selva Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Ashworth, Alan. The Institute Of Cancer Research; Reino Unido
Fil: Sakamoto, Kei. University Of Dundee; Reino Unido
Fil: Hardie, D. Grahame. University Of Dundee; Reino Unido
Materia
AMP-ACTIVATED PROTEIN KINASE (AMPK)
LKB1
MALE FERTILITY
SPERMIOGENESIS
SPLICE VARIANTS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/216612
Acceder
id CONICETDig_42a01abf852332f14404261001ecb0b2
oai_identifier_str oai:ri.conicet.gov.ar:11336/216612
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A novel short splice variant of the tumour suppressor LKB1 is required for spermiogenesisTowler, Mhairi C.Fogarty, SarahHawley, Simon A.Pan, David A.Martin, David M. A.Morrice, Nicolas A.McCarthy, AfshanGalardo, Maria Noel LujanMeroni, Silvina BeatrizCigorraga, Selva BeatrizAshworth, AlanSakamoto, KeiHardie, D. GrahameAMP-ACTIVATED PROTEIN KINASE (AMPK)LKB1MALE FERTILITYSPERMIOGENESISSPLICE VARIANTShttps://purl.org/becyt/ford/3.5https://purl.org/becyt/ford/3LKB1 was discovered as a tumour suppressor mutated in Peutz-Jeghers syndrome, and is a gene involved in cell polarity as well as an upstream protein kinase for members of the AMP-activated protein kinase family. We report that mammals express two splice variants caused by alternate usage of 3′-exons. LKB1L is the previously described form, while LKB1s is a novel form in which the last 63 residues are replaced by a unique 39-residue sequence lacking known phosphorylation (Ser431) and farnesylation (Cys433) sites. Both isoforms are widely expressed in rodent and human tissues, although LKB1s is particularly abundant in haploid spermatids in the testis. Male mice in which expression of Lkb1s is knocked out are sterile, with the number of mature spermatozoa in the epididymis being dramatically reduced, and those spermatozoa that are produced have heads with an abnormal morphology and are non-motile. These results identify a previously undetected variant of LKB1, and suggest that it has a crucial role in spermiogenesis and male fertility.Fil: Towler, Mhairi C.. University Of Dundee; Reino UnidoFil: Fogarty, Sarah. University Of Dundee; Reino UnidoFil: Hawley, Simon A.. University Of Dundee; Reino UnidoFil: Pan, David A.. University Of Dundee; Reino UnidoFil: Martin, David M. A.. University Of Dundee; Reino UnidoFil: Morrice, Nicolas A.. University Of Dundee; Reino UnidoFil: McCarthy, Afshan. The Institute Of Cancer Research; Reino UnidoFil: Galardo, Maria Noel Lujan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Meroni, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Cigorraga, Selva Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Ashworth, Alan. The Institute Of Cancer Research; Reino UnidoFil: Sakamoto, Kei. University Of Dundee; Reino UnidoFil: Hardie, D. Grahame. University Of Dundee; Reino UnidoPortland Press2008-12info: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/11336/216612Towler, Mhairi C.; Fogarty, Sarah; Hawley, Simon A.; Pan, David A.; Martin, David M. A.; et al.; A novel short splice variant of the tumour suppressor LKB1 is required for spermiogenesis; Portland Press; Biochemical Journal; 416; 1; 12-2008; 1-140264-6021CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://portlandpress.com/biochemj/article-abstract/416/1/1/44482/A-novel-short-splice-variant-of-the-tumourinfo:eu-repo/semantics/altIdentifier/doi/10.1042/BJ20081447info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-29T11:20:16Zoai:ri.conicet.gov.ar:11336/216612instacron: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:34982025-10-29 11:20:16.518CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A novel short splice variant of the tumour suppressor LKB1 is required for spermiogenesis
title A novel short splice variant of the tumour suppressor LKB1 is required for spermiogenesis
spellingShingle A novel short splice variant of the tumour suppressor LKB1 is required for spermiogenesis
Towler, Mhairi C.
AMP-ACTIVATED PROTEIN KINASE (AMPK)
LKB1
MALE FERTILITY
SPERMIOGENESIS
SPLICE VARIANTS
title_short A novel short splice variant of the tumour suppressor LKB1 is required for spermiogenesis
title_full A novel short splice variant of the tumour suppressor LKB1 is required for spermiogenesis
title_fullStr A novel short splice variant of the tumour suppressor LKB1 is required for spermiogenesis
title_full_unstemmed A novel short splice variant of the tumour suppressor LKB1 is required for spermiogenesis
title_sort A novel short splice variant of the tumour suppressor LKB1 is required for spermiogenesis
dc.creator.none.fl_str_mv Towler, Mhairi C.
Fogarty, Sarah
Hawley, Simon A.
Pan, David A.
Martin, David M. A.
Morrice, Nicolas A.
McCarthy, Afshan
Galardo, Maria Noel Lujan
Meroni, Silvina Beatriz
Cigorraga, Selva Beatriz
Ashworth, Alan
Sakamoto, Kei
Hardie, D. Grahame
author Towler, Mhairi C.
author_facet Towler, Mhairi C.
Fogarty, Sarah
Hawley, Simon A.
Pan, David A.
Martin, David M. A.
Morrice, Nicolas A.
McCarthy, Afshan
Galardo, Maria Noel Lujan
Meroni, Silvina Beatriz
Cigorraga, Selva Beatriz
Ashworth, Alan
Sakamoto, Kei
Hardie, D. Grahame
author_role author
author2 Fogarty, Sarah
Hawley, Simon A.
Pan, David A.
Martin, David M. A.
Morrice, Nicolas A.
McCarthy, Afshan
Galardo, Maria Noel Lujan
Meroni, Silvina Beatriz
Cigorraga, Selva Beatriz
Ashworth, Alan
Sakamoto, Kei
Hardie, D. Grahame
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AMP-ACTIVATED PROTEIN KINASE (AMPK)
LKB1
MALE FERTILITY
SPERMIOGENESIS
SPLICE VARIANTS
topic AMP-ACTIVATED PROTEIN KINASE (AMPK)
LKB1
MALE FERTILITY
SPERMIOGENESIS
SPLICE VARIANTS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.5
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv LKB1 was discovered as a tumour suppressor mutated in Peutz-Jeghers syndrome, and is a gene involved in cell polarity as well as an upstream protein kinase for members of the AMP-activated protein kinase family. We report that mammals express two splice variants caused by alternate usage of 3′-exons. LKB1L is the previously described form, while LKB1s is a novel form in which the last 63 residues are replaced by a unique 39-residue sequence lacking known phosphorylation (Ser431) and farnesylation (Cys433) sites. Both isoforms are widely expressed in rodent and human tissues, although LKB1s is particularly abundant in haploid spermatids in the testis. Male mice in which expression of Lkb1s is knocked out are sterile, with the number of mature spermatozoa in the epididymis being dramatically reduced, and those spermatozoa that are produced have heads with an abnormal morphology and are non-motile. These results identify a previously undetected variant of LKB1, and suggest that it has a crucial role in spermiogenesis and male fertility.
Fil: Towler, Mhairi C.. University Of Dundee; Reino Unido
Fil: Fogarty, Sarah. University Of Dundee; Reino Unido
Fil: Hawley, Simon A.. University Of Dundee; Reino Unido
Fil: Pan, David A.. University Of Dundee; Reino Unido
Fil: Martin, David M. A.. University Of Dundee; Reino Unido
Fil: Morrice, Nicolas A.. University Of Dundee; Reino Unido
Fil: McCarthy, Afshan. The Institute Of Cancer Research; Reino Unido
Fil: Galardo, Maria Noel Lujan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Meroni, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Cigorraga, Selva Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Ashworth, Alan. The Institute Of Cancer Research; Reino Unido
Fil: Sakamoto, Kei. University Of Dundee; Reino Unido
Fil: Hardie, D. Grahame. University Of Dundee; Reino Unido
description LKB1 was discovered as a tumour suppressor mutated in Peutz-Jeghers syndrome, and is a gene involved in cell polarity as well as an upstream protein kinase for members of the AMP-activated protein kinase family. We report that mammals express two splice variants caused by alternate usage of 3′-exons. LKB1L is the previously described form, while LKB1s is a novel form in which the last 63 residues are replaced by a unique 39-residue sequence lacking known phosphorylation (Ser431) and farnesylation (Cys433) sites. Both isoforms are widely expressed in rodent and human tissues, although LKB1s is particularly abundant in haploid spermatids in the testis. Male mice in which expression of Lkb1s is knocked out are sterile, with the number of mature spermatozoa in the epididymis being dramatically reduced, and those spermatozoa that are produced have heads with an abnormal morphology and are non-motile. These results identify a previously undetected variant of LKB1, and suggest that it has a crucial role in spermiogenesis and male fertility.
publishDate 2008
dc.date.none.fl_str_mv 2008-12
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/11336/216612
Towler, Mhairi C.; Fogarty, Sarah; Hawley, Simon A.; Pan, David A.; Martin, David M. A.; et al.; A novel short splice variant of the tumour suppressor LKB1 is required for spermiogenesis; Portland Press; Biochemical Journal; 416; 1; 12-2008; 1-14
0264-6021
CONICET Digital
CONICET
url http://hdl.handle.net/11336/216612
identifier_str_mv Towler, Mhairi C.; Fogarty, Sarah; Hawley, Simon A.; Pan, David A.; Martin, David M. A.; et al.; A novel short splice variant of the tumour suppressor LKB1 is required for spermiogenesis; Portland Press; Biochemical Journal; 416; 1; 12-2008; 1-14
0264-6021
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://portlandpress.com/biochemj/article-abstract/416/1/1/44482/A-novel-short-splice-variant-of-the-tumour
info:eu-repo/semantics/altIdentifier/doi/10.1042/BJ20081447
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 Portland Press
publisher.none.fl_str_mv Portland Press
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
_version_ 1847426135753752576
score 13.10058

Publicaciones similares