Biosynthesis of the major brain gangliosides GD1a and GT1b

Autores
Sturgill, Elizabeth R.; Aoki, Kazuhiro; Lopez, Pablo; Colacurcio, Daniel; Vajn, Katarina; Lorenzini, Ileana; Majic, Senka; Yang, Won Ho; Heffer, Marija; Tiemeyer, Michael; Marth, Jamey D.; Schnaar, Ronald L.
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Gangliosides-sialylated glycosphingolipids-are the major glycoconjugates of nerve cells. The same four structures-GM1, GD1a, GD1b and GT1b-comprise the great majority of gangliosides in mammalian brains. They share a common tetrasaccharide core (Gal1-3GalNAc1-4Gal1-4Glc1-1′Cer) with one or two sialic acids on the internal galactose and zero (GM1 and GD1b) or one (GD1a and GT1b) 2-3-linked sialic acid on the terminal galactose. Whereas the genes responsible for the sialylation of the internal galactose are known, those responsible for terminal sialylation have not been established in vivo. We report that St3gal2 and St3gal3 are responsible for nearly all the terminal sialylation of brain gangliosides in the mouse. When brain ganglioside expression was analyzed in adult St3gal1-, St3gal2-, St3gal3-and St3gal4-null mice, only St3gal2-null mice differed significantly from wild type, expressing half the normal amount of GD1a and GT1b. St3gal1/2-double-null mice were no different than St3gal2-single-null mice; however, St3gal2/3-double-null mice were >95 depleted in gangliosides GD1a and GT1b. Total ganglioside expression (lipid-bound sialic acid) in the brains of St3gal2/3-double-null mice was equivalent to that in wild-type mice, whereas total protein sialylation was reduced by half. St3gal2/3-double-null mice were small, weak and short lived. They were half the weight of wild-type mice at weaning and displayed early hindlimb dysreflexia. We conclude that the St3gal2 and St3gal3 gene products (ST3Gal-II and ST3Gal-III sialyltransferases) are largely responsible for ganglioside terminal 2-3 sialylation in the brain, synthesizing the major brain gangliosides GD1a and GT1b. © 2012 The Author.
Fil: Sturgill, Elizabeth R.. Johns Hopkins School Of Medicine; Estados Unidos. University Johns Hopkins; Estados Unidos
Fil: Aoki, Kazuhiro. University of Georgia; Estados Unidos
Fil: Lopez, Pablo. University Johns Hopkins; Estados Unidos
Fil: Colacurcio, Daniel. University Johns Hopkins; Estados Unidos
Fil: Vajn, Katarina. University Johns Hopkins; Estados Unidos
Fil: Lorenzini, Ileana. University Johns Hopkins; Estados Unidos
Fil: Majic, Senka. University Johns Hopkins; Estados Unidos
Fil: Yang, Won Ho. University of California; Estados Unidos
Fil: Heffer, Marija. J. J. Strossmayer University; Croacia
Fil: Tiemeyer, Michael. University of Georgia; Estados Unidos
Fil: Marth, Jamey D.. University of California; Estados Unidos
Fil: Schnaar, Ronald L.. University Johns Hopkins; Estados Unidos
Materia
BRAIN
GANGLIOSIDE
MYELIN
SIALIC ACID
SIALYLTRANSFERASE
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:11336/197563

id CONICETDig_5006e08af86daccb5f0dd5773b16e197
oai_identifier_str oai:ri.conicet.gov.ar:11336/197563
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Biosynthesis of the major brain gangliosides GD1a and GT1bSturgill, Elizabeth R.Aoki, KazuhiroLopez, PabloColacurcio, DanielVajn, KatarinaLorenzini, IleanaMajic, SenkaYang, Won HoHeffer, MarijaTiemeyer, MichaelMarth, Jamey D.Schnaar, Ronald L.BRAINGANGLIOSIDEMYELINSIALIC ACIDSIALYLTRANSFERASEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Gangliosides-sialylated glycosphingolipids-are the major glycoconjugates of nerve cells. The same four structures-GM1, GD1a, GD1b and GT1b-comprise the great majority of gangliosides in mammalian brains. They share a common tetrasaccharide core (Gal1-3GalNAc1-4Gal1-4Glc1-1′Cer) with one or two sialic acids on the internal galactose and zero (GM1 and GD1b) or one (GD1a and GT1b) 2-3-linked sialic acid on the terminal galactose. Whereas the genes responsible for the sialylation of the internal galactose are known, those responsible for terminal sialylation have not been established in vivo. We report that St3gal2 and St3gal3 are responsible for nearly all the terminal sialylation of brain gangliosides in the mouse. When brain ganglioside expression was analyzed in adult St3gal1-, St3gal2-, St3gal3-and St3gal4-null mice, only St3gal2-null mice differed significantly from wild type, expressing half the normal amount of GD1a and GT1b. St3gal1/2-double-null mice were no different than St3gal2-single-null mice; however, St3gal2/3-double-null mice were >95 depleted in gangliosides GD1a and GT1b. Total ganglioside expression (lipid-bound sialic acid) in the brains of St3gal2/3-double-null mice was equivalent to that in wild-type mice, whereas total protein sialylation was reduced by half. St3gal2/3-double-null mice were small, weak and short lived. They were half the weight of wild-type mice at weaning and displayed early hindlimb dysreflexia. We conclude that the St3gal2 and St3gal3 gene products (ST3Gal-II and ST3Gal-III sialyltransferases) are largely responsible for ganglioside terminal 2-3 sialylation in the brain, synthesizing the major brain gangliosides GD1a and GT1b. © 2012 The Author.Fil: Sturgill, Elizabeth R.. Johns Hopkins School Of Medicine; Estados Unidos. University Johns Hopkins; Estados UnidosFil: Aoki, Kazuhiro. University of Georgia; Estados UnidosFil: Lopez, Pablo. University Johns Hopkins; Estados UnidosFil: Colacurcio, Daniel. University Johns Hopkins; Estados UnidosFil: Vajn, Katarina. University Johns Hopkins; Estados UnidosFil: Lorenzini, Ileana. University Johns Hopkins; Estados UnidosFil: Majic, Senka. University Johns Hopkins; Estados UnidosFil: Yang, Won Ho. University of California; Estados UnidosFil: Heffer, Marija. J. J. Strossmayer University; CroaciaFil: Tiemeyer, Michael. University of Georgia; Estados UnidosFil: Marth, Jamey D.. University of California; Estados UnidosFil: Schnaar, Ronald L.. University Johns Hopkins; Estados UnidosOxford Univ Press Inc2012-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/197563Sturgill, Elizabeth R.; Aoki, Kazuhiro; Lopez, Pablo; Colacurcio, Daniel; Vajn, Katarina; et al.; Biosynthesis of the major brain gangliosides GD1a and GT1b; Oxford Univ Press Inc; Glycobiology; 22; 10; 10-2012; 1289-13010959-66581460-2423CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1093/glycob/cws103info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/glycob/article/22/10/1289/1988226info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:10:47Zoai:ri.conicet.gov.ar:11336/197563instacron: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:34982025-09-03 10:10:47.862CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Biosynthesis of the major brain gangliosides GD1a and GT1b
title Biosynthesis of the major brain gangliosides GD1a and GT1b
spellingShingle Biosynthesis of the major brain gangliosides GD1a and GT1b
Sturgill, Elizabeth R.
BRAIN
GANGLIOSIDE
MYELIN
SIALIC ACID
SIALYLTRANSFERASE
title_short Biosynthesis of the major brain gangliosides GD1a and GT1b
title_full Biosynthesis of the major brain gangliosides GD1a and GT1b
title_fullStr Biosynthesis of the major brain gangliosides GD1a and GT1b
title_full_unstemmed Biosynthesis of the major brain gangliosides GD1a and GT1b
title_sort Biosynthesis of the major brain gangliosides GD1a and GT1b
dc.creator.none.fl_str_mv Sturgill, Elizabeth R.
Aoki, Kazuhiro
Lopez, Pablo
Colacurcio, Daniel
Vajn, Katarina
Lorenzini, Ileana
Majic, Senka
Yang, Won Ho
Heffer, Marija
Tiemeyer, Michael
Marth, Jamey D.
Schnaar, Ronald L.
author Sturgill, Elizabeth R.
author_facet Sturgill, Elizabeth R.
Aoki, Kazuhiro
Lopez, Pablo
Colacurcio, Daniel
Vajn, Katarina
Lorenzini, Ileana
Majic, Senka
Yang, Won Ho
Heffer, Marija
Tiemeyer, Michael
Marth, Jamey D.
Schnaar, Ronald L.
author_role author
author2 Aoki, Kazuhiro
Lopez, Pablo
Colacurcio, Daniel
Vajn, Katarina
Lorenzini, Ileana
Majic, Senka
Yang, Won Ho
Heffer, Marija
Tiemeyer, Michael
Marth, Jamey D.
Schnaar, Ronald L.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BRAIN
GANGLIOSIDE
MYELIN
SIALIC ACID
SIALYLTRANSFERASE
topic BRAIN
GANGLIOSIDE
MYELIN
SIALIC ACID
SIALYLTRANSFERASE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Gangliosides-sialylated glycosphingolipids-are the major glycoconjugates of nerve cells. The same four structures-GM1, GD1a, GD1b and GT1b-comprise the great majority of gangliosides in mammalian brains. They share a common tetrasaccharide core (Gal1-3GalNAc1-4Gal1-4Glc1-1′Cer) with one or two sialic acids on the internal galactose and zero (GM1 and GD1b) or one (GD1a and GT1b) 2-3-linked sialic acid on the terminal galactose. Whereas the genes responsible for the sialylation of the internal galactose are known, those responsible for terminal sialylation have not been established in vivo. We report that St3gal2 and St3gal3 are responsible for nearly all the terminal sialylation of brain gangliosides in the mouse. When brain ganglioside expression was analyzed in adult St3gal1-, St3gal2-, St3gal3-and St3gal4-null mice, only St3gal2-null mice differed significantly from wild type, expressing half the normal amount of GD1a and GT1b. St3gal1/2-double-null mice were no different than St3gal2-single-null mice; however, St3gal2/3-double-null mice were >95 depleted in gangliosides GD1a and GT1b. Total ganglioside expression (lipid-bound sialic acid) in the brains of St3gal2/3-double-null mice was equivalent to that in wild-type mice, whereas total protein sialylation was reduced by half. St3gal2/3-double-null mice were small, weak and short lived. They were half the weight of wild-type mice at weaning and displayed early hindlimb dysreflexia. We conclude that the St3gal2 and St3gal3 gene products (ST3Gal-II and ST3Gal-III sialyltransferases) are largely responsible for ganglioside terminal 2-3 sialylation in the brain, synthesizing the major brain gangliosides GD1a and GT1b. © 2012 The Author.
Fil: Sturgill, Elizabeth R.. Johns Hopkins School Of Medicine; Estados Unidos. University Johns Hopkins; Estados Unidos
Fil: Aoki, Kazuhiro. University of Georgia; Estados Unidos
Fil: Lopez, Pablo. University Johns Hopkins; Estados Unidos
Fil: Colacurcio, Daniel. University Johns Hopkins; Estados Unidos
Fil: Vajn, Katarina. University Johns Hopkins; Estados Unidos
Fil: Lorenzini, Ileana. University Johns Hopkins; Estados Unidos
Fil: Majic, Senka. University Johns Hopkins; Estados Unidos
Fil: Yang, Won Ho. University of California; Estados Unidos
Fil: Heffer, Marija. J. J. Strossmayer University; Croacia
Fil: Tiemeyer, Michael. University of Georgia; Estados Unidos
Fil: Marth, Jamey D.. University of California; Estados Unidos
Fil: Schnaar, Ronald L.. University Johns Hopkins; Estados Unidos
description Gangliosides-sialylated glycosphingolipids-are the major glycoconjugates of nerve cells. The same four structures-GM1, GD1a, GD1b and GT1b-comprise the great majority of gangliosides in mammalian brains. They share a common tetrasaccharide core (Gal1-3GalNAc1-4Gal1-4Glc1-1′Cer) with one or two sialic acids on the internal galactose and zero (GM1 and GD1b) or one (GD1a and GT1b) 2-3-linked sialic acid on the terminal galactose. Whereas the genes responsible for the sialylation of the internal galactose are known, those responsible for terminal sialylation have not been established in vivo. We report that St3gal2 and St3gal3 are responsible for nearly all the terminal sialylation of brain gangliosides in the mouse. When brain ganglioside expression was analyzed in adult St3gal1-, St3gal2-, St3gal3-and St3gal4-null mice, only St3gal2-null mice differed significantly from wild type, expressing half the normal amount of GD1a and GT1b. St3gal1/2-double-null mice were no different than St3gal2-single-null mice; however, St3gal2/3-double-null mice were >95 depleted in gangliosides GD1a and GT1b. Total ganglioside expression (lipid-bound sialic acid) in the brains of St3gal2/3-double-null mice was equivalent to that in wild-type mice, whereas total protein sialylation was reduced by half. St3gal2/3-double-null mice were small, weak and short lived. They were half the weight of wild-type mice at weaning and displayed early hindlimb dysreflexia. We conclude that the St3gal2 and St3gal3 gene products (ST3Gal-II and ST3Gal-III sialyltransferases) are largely responsible for ganglioside terminal 2-3 sialylation in the brain, synthesizing the major brain gangliosides GD1a and GT1b. © 2012 The Author.
publishDate 2012
dc.date.none.fl_str_mv 2012-10
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/11336/197563
Sturgill, Elizabeth R.; Aoki, Kazuhiro; Lopez, Pablo; Colacurcio, Daniel; Vajn, Katarina; et al.; Biosynthesis of the major brain gangliosides GD1a and GT1b; Oxford Univ Press Inc; Glycobiology; 22; 10; 10-2012; 1289-1301
0959-6658
1460-2423
CONICET Digital
CONICET
url http://hdl.handle.net/11336/197563
identifier_str_mv Sturgill, Elizabeth R.; Aoki, Kazuhiro; Lopez, Pablo; Colacurcio, Daniel; Vajn, Katarina; et al.; Biosynthesis of the major brain gangliosides GD1a and GT1b; Oxford Univ Press Inc; Glycobiology; 22; 10; 10-2012; 1289-1301
0959-6658
1460-2423
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1093/glycob/cws103
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/glycob/article/22/10/1289/1988226
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
dc.publisher.none.fl_str_mv Oxford Univ Press Inc
publisher.none.fl_str_mv Oxford Univ Press Inc
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_ 1842270132454293504
score 13.13397