Neuronal glycoprotein M6a induces filopodia formation via association with cholesterol-rich lipid rafts.
J Neurochem
; 119(3): 521-31, 2011 Nov.
Article
em En
| MEDLINE
| ID: mdl-21426347
ABSTRACT
A neuronal integral membrane glycoprotein M6a has been suggested to be involved in a number of biological processes, including neuronal remodeling and differentiation, trafficking of mu-opioid receptors, and Ca(2+) transportation. Moreover, pathological situations such as chronic stress in animals and depression in humans have been associated with alterations in M6a sequence and expression. The mechanism of action of M6a is essentially unknown. In this work, we analyze the relevance of M6a distribution in plasma membrane, namely its lipid microdomain targeting, for its biological function in filopodia formation. We demonstrate that M6a is localized in membrane microdomains compatible with lipid rafts in cultured rat hippocampal neurons. Removal of cholesterol from neuronal membranes with methyl-ß-cyclodextrin decreases M6a-induced filopodia formation, an effect that is reversed by the addition of cholesterol. Inhibition of Src kinases and MAPK prevents filopodia formation in M6a-over-expressing neurons. Src-deficient SYF cells over-expressing M6a fail to promote filopodia formation. Taken together, our findings reveal that the association of M6a with lipid rafts is important for its role in filopodia formation and Src and MAPK kinases participate in M6a signal propagation.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Pseudópodes
/
Glicoproteínas de Membrana
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Colesterol
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Microdomínios da Membrana
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Proteínas do Tecido Nervoso
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Neurônios
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
J Neurochem
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Argentina