The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-mediated endocytosis and affects neuronal synapses

Autores
García, Micaela Diana; Formoso, Karina; Aparicio, Gabriela Inés; Frasch, Alberto Carlos C.; Scorticati, Camila
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Single point mutations or variations in the expression of the gene encoding theneuronal glycoprotein M6a have been associated with psychiatric disorders such as Alzheimer, depression and schizophrenia. In cultured neurons, M6a positivelycontributes to neurite extension, axon guidance, filopodia/spines outgrowth andsynapses formation. Endocytic processes of the neuronal membrane proteins arelinked to differentiation, growth, signalling and neuronal plasticity. However, the precise mechanism in which M6a internalize and recycle back to the neuronal membrane and its roles are unknown. Here we show, by using controlled in vitro assay, that if 40 % of M6a is endocytosed drastically decreased the number of synapses in hippocampal neurons at 15 days in culture. By re-establishing the levels of M6a at cell surface, up to more than 80 %, the number of synapses returned to its normal values. Furthermore, M6a internalization involves cathrin-coated pits probably by the association between the adaptor protein 2, AP-2, with the 251YEDI254 ?tyrosine based? motif located within M6a C-tail. Upon endocytosis, M6a sorted to EEA1 and Rab5 positive endosomes and afterwards can be sorted back to cell surface via Rab11 positive endosomes or conducted 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 the synapses without altering the protein levels ofsynaptophysin and N-methyl-D-aspartate receptor type-1 (NMDA-R1). This novelmechanism might be relevant during the neuronal development, pruning and/or in many mental disorders in which the number of synapses are affected
Fil: García, Micaela Diana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; Argentina
Fil: Formoso, Karina. Universidad Catolica Argentina; Argentina
Fil: Aparicio, Gabriela Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; Argentina
Fil: Frasch, Alberto Carlos C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; Argentina
Fil: Scorticati, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; Argentina
Materia
Plp Protein Family
Traffic
Endosomal Comparments
Neuronal Plasticity
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/49495
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/49495
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-mediated endocytosis and affects neuronal synapsesGarcía, Micaela DianaFormoso, KarinaAparicio, Gabriela InésFrasch, Alberto Carlos C.Scorticati, CamilaPlp Protein FamilyTrafficEndosomal ComparmentsNeuronal Plasticityhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Single point mutations or variations in the expression of the gene encoding theneuronal glycoprotein M6a have been associated with psychiatric disorders such as Alzheimer, depression and schizophrenia. In cultured neurons, M6a positivelycontributes to neurite extension, axon guidance, filopodia/spines outgrowth andsynapses formation. Endocytic processes of the neuronal membrane proteins arelinked to differentiation, growth, signalling and neuronal plasticity. However, the precise mechanism in which M6a internalize and recycle back to the neuronal membrane and its roles are unknown. Here we show, by using controlled in vitro assay, that if 40 % of M6a is endocytosed drastically decreased the number of synapses in hippocampal neurons at 15 days in culture. By re-establishing the levels of M6a at cell surface, up to more than 80 %, the number of synapses returned to its normal values. Furthermore, M6a internalization involves cathrin-coated pits probably by the association between the adaptor protein 2, AP-2, with the 251YEDI254 ?tyrosine based? motif located within M6a C-tail. Upon endocytosis, M6a sorted to EEA1 and Rab5 positive endosomes and afterwards can be sorted back to cell surface via Rab11 positive endosomes or conducted 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 the synapses without altering the protein levels ofsynaptophysin and N-methyl-D-aspartate receptor type-1 (NMDA-R1). This novelmechanism might be relevant during the neuronal development, pruning and/or in many mental disorders in which the number of synapses are affectedFil: García, Micaela Diana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; ArgentinaFil: Formoso, Karina. Universidad Catolica Argentina; ArgentinaFil: Aparicio, Gabriela Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; ArgentinaFil: Frasch, Alberto Carlos C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; ArgentinaFil: Scorticati, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; ArgentinaFrontiers Editorial Office2017-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/49495García, Micaela Diana; Formoso, Karina; Aparicio, Gabriela Inés; Frasch, Alberto Carlos C.; Scorticati, Camila; The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-mediated endocytosis and affects neuronal synapses; Frontiers Editorial Office; Frontiers in Molecular Neuroscience; 9-2017; 1-171674-2788CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fnmol.2017.00296info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fnmol.2017.00296/fullinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:23:17Zoai:ri.conicet.gov.ar:11336/49495instacron: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:34982025-10-15 14:23:17.439CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-mediated endocytosis and affects neuronal synapses
title The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-mediated endocytosis and affects neuronal synapses
spellingShingle The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-mediated endocytosis and affects neuronal synapses
García, Micaela Diana
Plp Protein Family
Traffic
Endosomal Comparments
Neuronal Plasticity
title_short The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-mediated endocytosis and affects neuronal synapses
title_full The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-mediated endocytosis and affects neuronal synapses
title_fullStr The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-mediated endocytosis and affects neuronal synapses
title_full_unstemmed The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-mediated endocytosis and affects neuronal synapses
title_sort The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-mediated endocytosis and affects neuronal synapses
dc.creator.none.fl_str_mv García, Micaela Diana
Formoso, Karina
Aparicio, Gabriela Inés
Frasch, Alberto Carlos C.
Scorticati, Camila
author García, Micaela Diana
author_facet García, Micaela Diana
Formoso, Karina
Aparicio, Gabriela Inés
Frasch, Alberto Carlos C.
Scorticati, Camila
author_role author
author2 Formoso, Karina
Aparicio, Gabriela Inés
Frasch, Alberto Carlos C.
Scorticati, Camila
author2_role author
author
author
author
dc.subject.none.fl_str_mv Plp Protein Family
Traffic
Endosomal Comparments
Neuronal Plasticity
topic Plp Protein Family
Traffic
Endosomal Comparments
Neuronal Plasticity
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Single point mutations or variations in the expression of the gene encoding theneuronal glycoprotein M6a have been associated with psychiatric disorders such as Alzheimer, depression and schizophrenia. In cultured neurons, M6a positivelycontributes to neurite extension, axon guidance, filopodia/spines outgrowth andsynapses formation. Endocytic processes of the neuronal membrane proteins arelinked to differentiation, growth, signalling and neuronal plasticity. However, the precise mechanism in which M6a internalize and recycle back to the neuronal membrane and its roles are unknown. Here we show, by using controlled in vitro assay, that if 40 % of M6a is endocytosed drastically decreased the number of synapses in hippocampal neurons at 15 days in culture. By re-establishing the levels of M6a at cell surface, up to more than 80 %, the number of synapses returned to its normal values. Furthermore, M6a internalization involves cathrin-coated pits probably by the association between the adaptor protein 2, AP-2, with the 251YEDI254 ?tyrosine based? motif located within M6a C-tail. Upon endocytosis, M6a sorted to EEA1 and Rab5 positive endosomes and afterwards can be sorted back to cell surface via Rab11 positive endosomes or conducted 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 the synapses without altering the protein levels ofsynaptophysin and N-methyl-D-aspartate receptor type-1 (NMDA-R1). This novelmechanism might be relevant during the neuronal development, pruning and/or in many mental disorders in which the number of synapses are affected
Fil: García, Micaela Diana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; Argentina
Fil: Formoso, Karina. Universidad Catolica Argentina; Argentina
Fil: Aparicio, Gabriela Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; Argentina
Fil: Frasch, Alberto Carlos C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; Argentina
Fil: Scorticati, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; Argentina
description Single point mutations or variations in the expression of the gene encoding theneuronal glycoprotein M6a have been associated with psychiatric disorders such as Alzheimer, depression and schizophrenia. In cultured neurons, M6a positivelycontributes to neurite extension, axon guidance, filopodia/spines outgrowth andsynapses formation. Endocytic processes of the neuronal membrane proteins arelinked to differentiation, growth, signalling and neuronal plasticity. However, the precise mechanism in which M6a internalize and recycle back to the neuronal membrane and its roles are unknown. Here we show, by using controlled in vitro assay, that if 40 % of M6a is endocytosed drastically decreased the number of synapses in hippocampal neurons at 15 days in culture. By re-establishing the levels of M6a at cell surface, up to more than 80 %, the number of synapses returned to its normal values. Furthermore, M6a internalization involves cathrin-coated pits probably by the association between the adaptor protein 2, AP-2, with the 251YEDI254 ?tyrosine based? motif located within M6a C-tail. Upon endocytosis, M6a sorted to EEA1 and Rab5 positive endosomes and afterwards can be sorted back to cell surface via Rab11 positive endosomes or conducted 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 the synapses without altering the protein levels ofsynaptophysin and N-methyl-D-aspartate receptor type-1 (NMDA-R1). This novelmechanism might be relevant during the neuronal development, pruning and/or in many mental disorders in which the number of synapses are affected
publishDate 2017
dc.date.none.fl_str_mv 2017-09
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/11336/49495
García, Micaela Diana; Formoso, Karina; Aparicio, Gabriela Inés; Frasch, Alberto Carlos C.; Scorticati, Camila; The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-mediated endocytosis and affects neuronal synapses; Frontiers Editorial Office; Frontiers in Molecular Neuroscience; 9-2017; 1-17
1674-2788
CONICET Digital
CONICET
url http://hdl.handle.net/11336/49495
identifier_str_mv García, Micaela Diana; Formoso, Karina; Aparicio, Gabriela Inés; Frasch, Alberto Carlos C.; Scorticati, Camila; The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-mediated endocytosis and affects neuronal synapses; Frontiers Editorial Office; Frontiers in Molecular Neuroscience; 9-2017; 1-17
1674-2788
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fnmol.2017.00296
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fnmol.2017.00296/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Editorial Office
publisher.none.fl_str_mv Frontiers Editorial Office
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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score 13.22299

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