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
Repositorio Institucional (UCA)
Institución
Pontificia Universidad Católica Argentina
OAI Identificador
oai:ucacris:123456789/8671

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oai_identifier_str oai:ucacris:123456789/8671
network_acronym_str RIUCA
repository_id_str 2585
network_name_str Repositorio Institucional (UCA)
spelling 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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