Glutamate slows axonal transport of neurofilaments in transfected neurons.
J Cell Biol
; 150(1): 165-76, 2000 Jul 10.
Article
em En
| MEDLINE
| ID: mdl-10893265
ABSTRACT
Neurofilaments are transported through axons by slow axonal transport. Abnormal accumulations of neurofilaments are seen in several neurodegenerative diseases, and this suggests that neurofilament transport is defective. Excitotoxic mechanisms involving glutamate are believed to be part of the pathogenic process in some neurodegenerative diseases, but there is currently little evidence to link glutamate with neurofilament transport. We have used a novel technique involving transfection of the green fluorescent protein-tagged neurofilament middle chain to measure neurofilament transport in cultured neurons. Treatment of the cells with glutamate induces a slowing of neurofilament transport. Phosphorylation of the side-arm domains of neurofilaments has been associated with a slowing of neurofilament transport, and we show that glutamate causes increased phosphorylation of these domains in cell bodies. We also show that glutamate activates members of the mitogen-activated protein kinase family, and that these kinases will phosphorylate neurofilament side-arm domains. These results provide a molecular framework to link glutamate excitotoxicity with neurofilament accumulation seen in some neurodegenerative diseases.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transporte Axonal
/
Proteínas de Neurofilamentos
/
Ácido Glutâmico
/
Neurônios
Limite:
Humans
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article