Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros










Base de dados
Tipo de estudo
Intervalo de ano de publicação
1.
J Neurosci ; 32(5): 1714-29, 2012 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-22302812

RESUMO

Numerous physiological functions, including a role as a cell surface receptor, have been ascribed to Alzheimer's disease-associated amyloid precursor protein (APP). However, detailed analysis of intracellular signaling mediated by APP in neurons has been lacking. Here, we characterized intrinsic signaling associated with membrane-bound APP C-terminal fragments, which are generated following APP ectodomain release by α- or ß-secretase cleavage. We found that accumulation of APP C-terminal fragments or expression of membrane-tethered APP intracellular domain results in adenylate cyclase-dependent activation of PKA (protein kinase A) and inhibition of GSK3ß signaling cascades, and enhancement of axodendritic arborization in rat immortalized hippocampal neurons, mouse primary cortical neurons, and mouse neuroblastoma. We discovered an interaction between BBXXB motif of APP intracellular domain and the heterotrimeric G-protein subunit Gα(S), and demonstrate that Gα(S) coupling to adenylate cyclase mediates membrane-tethered APP intracellular domain-induced neurite outgrowth. Our study provides clear evidence that APP intracellular domain can have a nontranscriptional role in regulating neurite outgrowth through its membrane association. The novel functional coupling of membrane-bound APP C-terminal fragments with Gα(S) signaling identified in this study could impact several brain functions such as synaptic plasticity and memory formation.


Assuntos
Precursor de Proteína beta-Amiloide/fisiologia , Subunidades alfa Gs de Proteínas de Ligação ao GTP/fisiologia , Membranas Intracelulares/fisiologia , Transdução de Sinais/fisiologia , Adenilil Ciclases/metabolismo , Adenilil Ciclases/fisiologia , Sequência de Aminoácidos , Precursor de Proteína beta-Amiloide/química , Animais , Células COS , Linhagem Celular Transformada , Linhagem Celular Tumoral , Membrana Celular/química , Membrana Celular/fisiologia , Proliferação de Células , Chlorocebus aethiops , Feminino , Subunidades alfa Gs de Proteínas de Ligação ao GTP/química , Membranas Intracelulares/química , Masculino , Camundongos , Dados de Sequência Molecular , Neuritos/fisiologia , Estrutura Terciária de Proteína , Ratos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...