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

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, ax...

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Detalles Bibliográficos
Autores principales: García, Micaela D., Formoso, Karina, Aparicio, Gabriela I., Frasch, Alberto C. C., Scorticati, Camila
Formato: Artículo
Lenguaje:Inglés
Publicado: Frontiers 2019
Materias:
NEURONAS
PROTEINAS
SINAPSIS
ENDOCITOSIS
PLASTICIDAD
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/8671
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-8671
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic NEURONAS
PROTEINAS
SINAPSIS
ENDOCITOSIS
PLASTICIDAD
spellingShingle NEURONAS
PROTEINAS
SINAPSIS
ENDOCITOSIS
PLASTICIDAD
García, Micaela D.
Formoso, Karina
Aparicio, Gabriela I.
Frasch, Alberto C. C.
Scorticati, Camila
The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-nediated endocytosis and affects neuronal synapses
topic_facet NEURONAS
PROTEINAS
SINAPSIS
ENDOCITOSIS
PLASTICIDAD
description 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.
format Artículo
author García, Micaela D.
Formoso, Karina
Aparicio, Gabriela I.
Frasch, Alberto C. C.
Scorticati, Camila
author_facet García, Micaela D.
Formoso, Karina
Aparicio, Gabriela I.
Frasch, Alberto C. C.
Scorticati, Camila
author_sort García, Micaela D.
title The membrane glycoprotein M6a endocytic/recycling pathway involves clathrin-nediated endocytosis and affects neuronal synapses
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 membrane glycoprotein m6a endocytic/recycling pathway involves clathrin-nediated endocytosis and affects neuronal synapses
publisher Frontiers
publishDate 2019
url https://repositorio.uca.edu.ar/handle/123456789/8671
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