Drosophila glial glutamate transporter Eaat1 is regulated by fringe-mediated notch signaling and is essential for larval locomotion

Autores
Stacey, Stephanie M.; Muraro, Nara Ines; Peco, Emilie; Labbe, Alain; Thomas, Graham B.; Baines, Richard A.; van Meyel, Donald J.
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In the mammalian CNS, glial cells expressing excitatory amino acid transporters (EAATs) tightly regulate extracellular glutamate levels to control neurotransmission and protect neurons from excitotoxic damage. Dysregulated EAAT expression is associated with several CNS pathologies in humans, yet mechanisms of EAAT regulation and the importance of glutamate transport for CNS development and function in vivo remain incompletely understood. Drosophila is an advanced genetic model with only a single high-affinity glutamate transporter termed Eaat1. We found that Eaat1 expression in CNS glia is regulated by the glycosyltransferase Fringe, which promotes neuron-to-glia signaling through the Delta-Notch ligand-receptor pair during embryogenesis. We made Eaat1 loss-of-function mutations and found that homozygous larvae could not perform the rhythmic peristaltic contractions required for crawling. We found no evidence for excitotoxic cell death or overt defects in the development of neurons and glia, and the crawling defect could be induced by postembryonic inactivation of Eaat1. Eaat1 fully rescued locomotor activity when expressed in only a limited subpopulation of glial cells situated near potential glutamatergic synapses within the CNS neuropil. Eaat1 mutants had deficits in the frequency, amplitude, and kinetics of synaptic currents in motor neurons whose rhythmic patterns of activity may be regulated by glutamatergic neurotransmission among premotor interneurons; similar results were seen with pharmacological manipulations of glutamate transport. Our findings indicate that Eaat1 expression is promoted by Fringe-mediated neuron-glial communication during development and suggest that Eaat1 plays an essential role in regulating CNS neural circuits that control locomotion in Drosophila.
Fil: Stacey, Stephanie M.. McGill University. Centre for Research in Neuroscience; Canadá
Fil: Muraro, Nara Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina. University Of Manchester; Reino Unido
Fil: Peco, Emilie. McGill University. Centre for Research in Neuroscience; Canadá
Fil: Labbe, Alain. McGill University. Centre for Research in Neuroscience; Canadá
Fil: Thomas, Graham B.. McGill University. Centre for Research in Neuroscience; Canadá
Fil: Baines, Richard A.. University Of Manchester; Reino Unido
Fil: van Meyel, Donald J.. McGill University. Centre for Research in Neuroscience; Canadá. McGill University. Department of Neurology and Neurosurgery; Canadá. McGill University. Health Centre Research Institute; Canadá
Materia
Drosophila melanogaster
Notch signaling
EAAT1
Glia
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:11336/14469

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oai_identifier_str oai:ri.conicet.gov.ar:11336/14469
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Drosophila glial glutamate transporter Eaat1 is regulated by fringe-mediated notch signaling and is essential for larval locomotionStacey, Stephanie M.Muraro, Nara InesPeco, EmilieLabbe, AlainThomas, Graham B.Baines, Richard A.van Meyel, Donald J.Drosophila melanogasterNotch signalingEAAT1Gliahttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1In the mammalian CNS, glial cells expressing excitatory amino acid transporters (EAATs) tightly regulate extracellular glutamate levels to control neurotransmission and protect neurons from excitotoxic damage. Dysregulated EAAT expression is associated with several CNS pathologies in humans, yet mechanisms of EAAT regulation and the importance of glutamate transport for CNS development and function in vivo remain incompletely understood. Drosophila is an advanced genetic model with only a single high-affinity glutamate transporter termed Eaat1. We found that Eaat1 expression in CNS glia is regulated by the glycosyltransferase Fringe, which promotes neuron-to-glia signaling through the Delta-Notch ligand-receptor pair during embryogenesis. We made Eaat1 loss-of-function mutations and found that homozygous larvae could not perform the rhythmic peristaltic contractions required for crawling. We found no evidence for excitotoxic cell death or overt defects in the development of neurons and glia, and the crawling defect could be induced by postembryonic inactivation of Eaat1. Eaat1 fully rescued locomotor activity when expressed in only a limited subpopulation of glial cells situated near potential glutamatergic synapses within the CNS neuropil. Eaat1 mutants had deficits in the frequency, amplitude, and kinetics of synaptic currents in motor neurons whose rhythmic patterns of activity may be regulated by glutamatergic neurotransmission among premotor interneurons; similar results were seen with pharmacological manipulations of glutamate transport. Our findings indicate that Eaat1 expression is promoted by Fringe-mediated neuron-glial communication during development and suggest that Eaat1 plays an essential role in regulating CNS neural circuits that control locomotion in Drosophila.Fil: Stacey, Stephanie M.. McGill University. Centre for Research in Neuroscience; CanadáFil: Muraro, Nara Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina. University Of Manchester; Reino UnidoFil: Peco, Emilie. McGill University. Centre for Research in Neuroscience; CanadáFil: Labbe, Alain. McGill University. Centre for Research in Neuroscience; CanadáFil: Thomas, Graham B.. McGill University. Centre for Research in Neuroscience; CanadáFil: Baines, Richard A.. University Of Manchester; Reino UnidoFil: van Meyel, Donald J.. McGill University. Centre for Research in Neuroscience; Canadá. McGill University. Department of Neurology and Neurosurgery; Canadá. McGill University. Health Centre Research Institute; CanadáSociety For Neuroscience2010-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/14469Stacey, Stephanie M.; Muraro, Nara Ines; Peco, Emilie; Labbe, Alain; Thomas, Graham B.; et al.; Drosophila glial glutamate transporter Eaat1 is regulated by fringe-mediated notch signaling and is essential for larval locomotion; Society For Neuroscience; Journal Of Neuroscience; 30; 43; 10-2010; 14446-144570270-6474enginfo:eu-repo/semantics/altIdentifier/url/http://www.jneurosci.org/content/30/43/14446.longinfo:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.1523/JNEUROSCI.1021-10.2010info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:01:11Zoai:ri.conicet.gov.ar:11336/14469instacron: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 10:01:11.689CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Drosophila glial glutamate transporter Eaat1 is regulated by fringe-mediated notch signaling and is essential for larval locomotion
title Drosophila glial glutamate transporter Eaat1 is regulated by fringe-mediated notch signaling and is essential for larval locomotion
spellingShingle Drosophila glial glutamate transporter Eaat1 is regulated by fringe-mediated notch signaling and is essential for larval locomotion
Stacey, Stephanie M.
Drosophila melanogaster
Notch signaling
EAAT1
Glia
title_short Drosophila glial glutamate transporter Eaat1 is regulated by fringe-mediated notch signaling and is essential for larval locomotion
title_full Drosophila glial glutamate transporter Eaat1 is regulated by fringe-mediated notch signaling and is essential for larval locomotion
title_fullStr Drosophila glial glutamate transporter Eaat1 is regulated by fringe-mediated notch signaling and is essential for larval locomotion
title_full_unstemmed Drosophila glial glutamate transporter Eaat1 is regulated by fringe-mediated notch signaling and is essential for larval locomotion
title_sort Drosophila glial glutamate transporter Eaat1 is regulated by fringe-mediated notch signaling and is essential for larval locomotion
dc.creator.none.fl_str_mv Stacey, Stephanie M.
Muraro, Nara Ines
Peco, Emilie
Labbe, Alain
Thomas, Graham B.
Baines, Richard A.
van Meyel, Donald J.
author Stacey, Stephanie M.
author_facet Stacey, Stephanie M.
Muraro, Nara Ines
Peco, Emilie
Labbe, Alain
Thomas, Graham B.
Baines, Richard A.
van Meyel, Donald J.
author_role author
author2 Muraro, Nara Ines
Peco, Emilie
Labbe, Alain
Thomas, Graham B.
Baines, Richard A.
van Meyel, Donald J.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Drosophila melanogaster
Notch signaling
EAAT1
Glia
topic Drosophila melanogaster
Notch signaling
EAAT1
Glia
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv In the mammalian CNS, glial cells expressing excitatory amino acid transporters (EAATs) tightly regulate extracellular glutamate levels to control neurotransmission and protect neurons from excitotoxic damage. Dysregulated EAAT expression is associated with several CNS pathologies in humans, yet mechanisms of EAAT regulation and the importance of glutamate transport for CNS development and function in vivo remain incompletely understood. Drosophila is an advanced genetic model with only a single high-affinity glutamate transporter termed Eaat1. We found that Eaat1 expression in CNS glia is regulated by the glycosyltransferase Fringe, which promotes neuron-to-glia signaling through the Delta-Notch ligand-receptor pair during embryogenesis. We made Eaat1 loss-of-function mutations and found that homozygous larvae could not perform the rhythmic peristaltic contractions required for crawling. We found no evidence for excitotoxic cell death or overt defects in the development of neurons and glia, and the crawling defect could be induced by postembryonic inactivation of Eaat1. Eaat1 fully rescued locomotor activity when expressed in only a limited subpopulation of glial cells situated near potential glutamatergic synapses within the CNS neuropil. Eaat1 mutants had deficits in the frequency, amplitude, and kinetics of synaptic currents in motor neurons whose rhythmic patterns of activity may be regulated by glutamatergic neurotransmission among premotor interneurons; similar results were seen with pharmacological manipulations of glutamate transport. Our findings indicate that Eaat1 expression is promoted by Fringe-mediated neuron-glial communication during development and suggest that Eaat1 plays an essential role in regulating CNS neural circuits that control locomotion in Drosophila.
Fil: Stacey, Stephanie M.. McGill University. Centre for Research in Neuroscience; Canadá
Fil: Muraro, Nara Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina. University Of Manchester; Reino Unido
Fil: Peco, Emilie. McGill University. Centre for Research in Neuroscience; Canadá
Fil: Labbe, Alain. McGill University. Centre for Research in Neuroscience; Canadá
Fil: Thomas, Graham B.. McGill University. Centre for Research in Neuroscience; Canadá
Fil: Baines, Richard A.. University Of Manchester; Reino Unido
Fil: van Meyel, Donald J.. McGill University. Centre for Research in Neuroscience; Canadá. McGill University. Department of Neurology and Neurosurgery; Canadá. McGill University. Health Centre Research Institute; Canadá
description In the mammalian CNS, glial cells expressing excitatory amino acid transporters (EAATs) tightly regulate extracellular glutamate levels to control neurotransmission and protect neurons from excitotoxic damage. Dysregulated EAAT expression is associated with several CNS pathologies in humans, yet mechanisms of EAAT regulation and the importance of glutamate transport for CNS development and function in vivo remain incompletely understood. Drosophila is an advanced genetic model with only a single high-affinity glutamate transporter termed Eaat1. We found that Eaat1 expression in CNS glia is regulated by the glycosyltransferase Fringe, which promotes neuron-to-glia signaling through the Delta-Notch ligand-receptor pair during embryogenesis. We made Eaat1 loss-of-function mutations and found that homozygous larvae could not perform the rhythmic peristaltic contractions required for crawling. We found no evidence for excitotoxic cell death or overt defects in the development of neurons and glia, and the crawling defect could be induced by postembryonic inactivation of Eaat1. Eaat1 fully rescued locomotor activity when expressed in only a limited subpopulation of glial cells situated near potential glutamatergic synapses within the CNS neuropil. Eaat1 mutants had deficits in the frequency, amplitude, and kinetics of synaptic currents in motor neurons whose rhythmic patterns of activity may be regulated by glutamatergic neurotransmission among premotor interneurons; similar results were seen with pharmacological manipulations of glutamate transport. Our findings indicate that Eaat1 expression is promoted by Fringe-mediated neuron-glial communication during development and suggest that Eaat1 plays an essential role in regulating CNS neural circuits that control locomotion in Drosophila.
publishDate 2010
dc.date.none.fl_str_mv 2010-10
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/11336/14469
Stacey, Stephanie M.; Muraro, Nara Ines; Peco, Emilie; Labbe, Alain; Thomas, Graham B.; et al.; Drosophila glial glutamate transporter Eaat1 is regulated by fringe-mediated notch signaling and is essential for larval locomotion; Society For Neuroscience; Journal Of Neuroscience; 30; 43; 10-2010; 14446-14457
0270-6474
url http://hdl.handle.net/11336/14469
identifier_str_mv Stacey, Stephanie M.; Muraro, Nara Ines; Peco, Emilie; Labbe, Alain; Thomas, Graham B.; et al.; Drosophila glial glutamate transporter Eaat1 is regulated by fringe-mediated notch signaling and is essential for larval locomotion; Society For Neuroscience; Journal Of Neuroscience; 30; 43; 10-2010; 14446-14457
0270-6474
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.jneurosci.org/content/30/43/14446.long
info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.1523/JNEUROSCI.1021-10.2010
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 Society For Neuroscience
publisher.none.fl_str_mv Society For Neuroscience
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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