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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/49495
Ver los metadatos del registro completo
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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 Técnicas2025-10-22T11:02:53Zoai: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:34982025-10-22 11:02:53.768CONICET 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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1846781248354123776 |
score |
12.982451 |