The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-nediated endocytosis and affects neuronal synapses
- Autores
- García, Micaela D.; Formoso, Karina; Aparicio, Gabriela I.; Frasch, Alberto C. C.; Scorticati, Camila
- Año de publicación
- 2017
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Fil: García, Micaela D. Universidad Nacional de San Martín. Instituto Tecnológico de Chascomús. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: García, Micaela D. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Formoso, Karina. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Aparicio, Gabriela I. Universidad Nacional de San Martín. Instituto Tecnológico de Chascomús. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Aparicio, Gabriela I. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Frasch, Alberto C. C. Universidad Nacional de San Martín. Instituto Tecnológico de Chascomús. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Scorticati, Camila. Universidad Nacional de San Martín. Instituto Tecnológico de Chascomús. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Scorticati, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Abstract: Single point mutations or variations in the expression of the gene encoding the neuronal glycoprotein M6a have been associated with psychiatric disorders such as Alzheimer's disease, depression and schizophrenia. In cultured neurons, M6a positively contributes to neurite extension, axon guidance, filopodia/spine outgrowth, and synapse formation. The endocytic processes of neuronal membrane proteins are linked to the differentiation, growth, signaling and plasticity of neurons. However, the roles of M6a and the precise mechanisms through which M6a internalizes and recycles back to the neuronal membrane are unknown. Here, by using a controlled in vitro assay, we showed that if 30-40% of M6a is endocytosed, the number of synapses in hippocampal neurons decreases. When re-establishing the levels of M6a at the cell surface, the number of synapses returned to normal values. M6a internalization involves clathrin-coated pits, probably by association between the adaptor protein 2 and the 251YEDI254 "tyrosine-based" motif located within the C-tail of M6a. Upon endocytosis, M6a is sorted to early endosome antigen 1- and Rab5-positive endosomes and then sorted back to the cell surface via Rab11-positive endosomes or to degradation via Rab7 and, finally LAMP-1-positive endosomes. Our results demonstrated that the levels of M6a at the cell surface modified the formation/maintenance of synapses, without altering the protein levels of synaptophysin or N-methyl-D-aspartate receptor type-1. This novel mechanism might be relevant during neuronal development, pruning and/or many of the neurological disorders in which the number of synapses is affected. - Fuente
- Frontiers in Molecular Neurosciencie 2017;10
- Materia
-
NEURONAS
PROTEINAS
SINAPSIS
ENDOCITOSIS
PLASTICIDAD - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/4.0/
- Repositorio
- Institución
- Pontificia Universidad Católica Argentina
- OAI Identificador
- oai:ucacris:123456789/8671
Ver los metadatos del registro completo
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The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-nediated endocytosis and affects neuronal synapsesGarcía, Micaela D.Formoso, KarinaAparicio, Gabriela I.Frasch, Alberto C. C.Scorticati, CamilaNEURONASPROTEINASSINAPSISENDOCITOSISPLASTICIDADFil: García, Micaela D. Universidad Nacional de San Martín. Instituto Tecnológico de Chascomús. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: García, Micaela D. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Formoso, Karina. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; ArgentinaFil: Aparicio, Gabriela I. Universidad Nacional de San Martín. Instituto Tecnológico de Chascomús. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Aparicio, Gabriela I. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Frasch, Alberto C. C. Universidad Nacional de San Martín. Instituto Tecnológico de Chascomús. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Scorticati, Camila. Universidad Nacional de San Martín. Instituto Tecnológico de Chascomús. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Scorticati, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAbstract: Single point mutations or variations in the expression of the gene encoding the neuronal glycoprotein M6a have been associated with psychiatric disorders such as Alzheimer's disease, depression and schizophrenia. In cultured neurons, M6a positively contributes to neurite extension, axon guidance, filopodia/spine outgrowth, and synapse formation. The endocytic processes of neuronal membrane proteins are linked to the differentiation, growth, signaling and plasticity of neurons. However, the roles of M6a and the precise mechanisms through which M6a internalizes and recycles back to the neuronal membrane are unknown. Here, by using a controlled in vitro assay, we showed that if 30-40% of M6a is endocytosed, the number of synapses in hippocampal neurons decreases. When re-establishing the levels of M6a at the cell surface, the number of synapses returned to normal values. M6a internalization involves clathrin-coated pits, probably by association between the adaptor protein 2 and the 251YEDI254 "tyrosine-based" motif located within the C-tail of M6a. Upon endocytosis, M6a is sorted to early endosome antigen 1- and Rab5-positive endosomes and then sorted back to the cell surface via Rab11-positive endosomes or to degradation via Rab7 and, finally LAMP-1-positive endosomes. Our results demonstrated that the levels of M6a at the cell surface modified the formation/maintenance of synapses, without altering the protein levels of synaptophysin or N-methyl-D-aspartate receptor type-1. This novel mechanism might be relevant during neuronal development, pruning and/or many of the neurological disorders in which the number of synapses is affected.Frontiers2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://repositorio.uca.edu.ar/handle/123456789/86711662-509910.3389/fnmol.2017.0029628979185Garcia MD, Formoso K, Aparicio GI, Frasch ACC, Scorticati C. The Membrane Glycoprotein M6a Endocytic/Recycling Pathway Involves Clathrin-Mediated Endocytosis and Affects Neuronal Synapses [en línea]. Frontiers in Molecular Neurosciencie 2017;10. doi:10.3389/fnmol.2017.00296 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/8671Frontiers in Molecular Neurosciencie 2017;10reponame:Repositorio Institucional (UCA)instname:Pontificia Universidad Católica Argentinaenginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/4.0/2025-07-03T10:56:52Zoai:ucacris:123456789/8671instacron:UCAInstitucionalhttps://repositorio.uca.edu.ar/Universidad privadaNo correspondehttps://repositorio.uca.edu.ar/oaiclaudia_fernandez@uca.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:25852025-07-03 10:56:52.634Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentinafalse |
dc.title.none.fl_str_mv |
The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-nediated endocytosis and affects neuronal synapses |
title |
The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-nediated endocytosis and affects neuronal synapses |
spellingShingle |
The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-nediated endocytosis and affects neuronal synapses García, Micaela D. NEURONAS PROTEINAS SINAPSIS ENDOCITOSIS PLASTICIDAD |
title_short |
The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-nediated endocytosis and affects neuronal synapses |
title_full |
The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-nediated endocytosis and affects neuronal synapses |
title_fullStr |
The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-nediated endocytosis and affects neuronal synapses |
title_full_unstemmed |
The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-nediated endocytosis and affects neuronal synapses |
title_sort |
The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-nediated endocytosis and affects neuronal synapses |
dc.creator.none.fl_str_mv |
García, Micaela D. Formoso, Karina Aparicio, Gabriela I. Frasch, Alberto C. C. Scorticati, Camila |
author |
García, Micaela D. |
author_facet |
García, Micaela D. Formoso, Karina Aparicio, Gabriela I. Frasch, Alberto C. C. Scorticati, Camila |
author_role |
author |
author2 |
Formoso, Karina Aparicio, Gabriela I. Frasch, Alberto C. C. Scorticati, Camila |
author2_role |
author author author author |
dc.subject.none.fl_str_mv |
NEURONAS PROTEINAS SINAPSIS ENDOCITOSIS PLASTICIDAD |
topic |
NEURONAS PROTEINAS SINAPSIS ENDOCITOSIS PLASTICIDAD |
dc.description.none.fl_txt_mv |
Fil: García, Micaela D. Universidad Nacional de San Martín. Instituto Tecnológico de Chascomús. Instituto de Investigaciones Biotecnológicas; Argentina Fil: García, Micaela D. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Formoso, Karina. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Aparicio, Gabriela I. Universidad Nacional de San Martín. Instituto Tecnológico de Chascomús. Instituto de Investigaciones Biotecnológicas; Argentina Fil: Aparicio, Gabriela I. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Frasch, Alberto C. C. Universidad Nacional de San Martín. Instituto Tecnológico de Chascomús. Instituto de Investigaciones Biotecnológicas; Argentina Fil: Scorticati, Camila. Universidad Nacional de San Martín. Instituto Tecnológico de Chascomús. Instituto de Investigaciones Biotecnológicas; Argentina Fil: Scorticati, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Abstract: Single point mutations or variations in the expression of the gene encoding the neuronal glycoprotein M6a have been associated with psychiatric disorders such as Alzheimer's disease, depression and schizophrenia. In cultured neurons, M6a positively contributes to neurite extension, axon guidance, filopodia/spine outgrowth, and synapse formation. The endocytic processes of neuronal membrane proteins are linked to the differentiation, growth, signaling and plasticity of neurons. However, the roles of M6a and the precise mechanisms through which M6a internalizes and recycles back to the neuronal membrane are unknown. Here, by using a controlled in vitro assay, we showed that if 30-40% of M6a is endocytosed, the number of synapses in hippocampal neurons decreases. When re-establishing the levels of M6a at the cell surface, the number of synapses returned to normal values. M6a internalization involves clathrin-coated pits, probably by association between the adaptor protein 2 and the 251YEDI254 "tyrosine-based" motif located within the C-tail of M6a. Upon endocytosis, M6a is sorted to early endosome antigen 1- and Rab5-positive endosomes and then sorted back to the cell surface via Rab11-positive endosomes or to degradation via Rab7 and, finally LAMP-1-positive endosomes. Our results demonstrated that the levels of M6a at the cell surface modified the formation/maintenance of synapses, without altering the protein levels of synaptophysin or N-methyl-D-aspartate receptor type-1. This novel mechanism might be relevant during neuronal development, pruning and/or many of the neurological disorders in which the number of synapses is affected. |
description |
Fil: García, Micaela D. Universidad Nacional de San Martín. Instituto Tecnológico de Chascomús. Instituto de Investigaciones Biotecnológicas; Argentina |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017 |
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 |
https://repositorio.uca.edu.ar/handle/123456789/8671 1662-5099 10.3389/fnmol.2017.00296 28979185 Garcia MD, Formoso K, Aparicio GI, Frasch ACC, Scorticati C. The Membrane Glycoprotein M6a Endocytic/Recycling Pathway Involves Clathrin-Mediated Endocytosis and Affects Neuronal Synapses [en línea]. Frontiers in Molecular Neurosciencie 2017;10. doi:10.3389/fnmol.2017.00296 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/8671 |
url |
https://repositorio.uca.edu.ar/handle/123456789/8671 |
identifier_str_mv |
1662-5099 10.3389/fnmol.2017.00296 28979185 Garcia MD, Formoso K, Aparicio GI, Frasch ACC, Scorticati C. The Membrane Glycoprotein M6a Endocytic/Recycling Pathway Involves Clathrin-Mediated Endocytosis and Affects Neuronal Synapses [en línea]. Frontiers in Molecular Neurosciencie 2017;10. doi:10.3389/fnmol.2017.00296 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/8671 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/4.0/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/4.0/ |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Frontiers |
publisher.none.fl_str_mv |
Frontiers |
dc.source.none.fl_str_mv |
Frontiers in Molecular Neurosciencie 2017;10 reponame:Repositorio Institucional (UCA) instname:Pontificia Universidad Católica Argentina |
reponame_str |
Repositorio Institucional (UCA) |
collection |
Repositorio Institucional (UCA) |
instname_str |
Pontificia Universidad Católica Argentina |
repository.name.fl_str_mv |
Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentina |
repository.mail.fl_str_mv |
claudia_fernandez@uca.edu.ar |
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1836638347455365120 |
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13.13397 |