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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/14469
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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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1844613802868342784 |
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13.070432 |