The neural cell adhesion molecule promotes maturation of the presynaptic endocytotic machinery by switching synaptic vesicle recycling from adaptor protein 3 (AP-3)- to AP-2-dependent mechanisms.
J Neurosci
; 33(42): 16828-45, 2013 Oct 16.
Article
em En
| MEDLINE
| ID: mdl-24133283
ABSTRACT
Newly formed synapses undergo maturation during ontogenetic development via mechanisms that remain poorly understood. We show that maturation of the presynaptic endocytotic machinery in CNS neurons requires substitution of the adaptor protein 3 (AP-3) with AP-2 at the presynaptic plasma membrane. In mature synapses, AP-2 associates with the intracellular domain of the neural cell adhesion molecule (NCAM). NCAM promotes binding of AP-2 over binding of AP-3 to presynaptic membranes, thus favoring the substitution of AP-3 for AP-2 during formation of mature synapses. The presynaptic endocytotic machinery remains immature in adult NCAM-deficient (NCAM-/-) mice accumulating AP-3 instead of AP-2 and its partner protein AP180 in synaptic membranes and vesicles. NCAM deficiency or disruption of the NCAM/AP-2 complex in wild-type (NCAM+/+) neurons by overexpression of AP-2 binding-defective mutant NCAM interferes with efficient retrieval of the synaptic vesicle v-SNARE synaptobrevin 2. Abnormalities in synaptic vesicle endocytosis and recycling may thus contribute to neurological disorders associated with mutations in NCAM.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Vesículas Sinápticas
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Terminações Pré-Sinápticas
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Moléculas de Adesão de Célula Nervosa
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Complexo 2 de Proteínas Adaptadoras
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Complexo 3 de Proteínas Adaptadoras
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Endocitose
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Neurosci
Ano de publicação:
2013
Tipo de documento:
Article