Synaptic clustering of PSD-95 is regulated by c-Abl through tyrosine phosphorylation.
J Neurosci
; 30(10): 3728-38, 2010 Mar 10.
Article
em En
| MEDLINE
| ID: mdl-20220006
ABSTRACT
The c-Abl tyrosine kinase is present in mouse brain synapses, but its precise synaptic function is unknown. We found that c-Abl levels in the rat hippocampus increase postnatally, with expression peaking at the first postnatal week. In 14 d in vitro hippocampal neuron cultures, c-Abl localizes primarily to the postsynaptic compartment, in which it colocalizes with the postsynaptic scaffold protein postsynaptic density protein-95 (PSD-95) in apposition to presynaptic markers. c-Abl associates with PSD-95, and chemical or genetic inhibition of c-Abl kinase activity reduces PSD-95 tyrosine phosphorylation, leading to reduced PSD-95 clustering and reduced synapses in treated neurons. c-Abl can phosphorylate PSD-95 on tyrosine 533, and mutation of this residue reduces the ability of PSD-95 to cluster at postsynaptic sites. Our results indicate that c-Abl regulates synapse formation by mediating tyrosine phosphorylation and clustering of PSD-95.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sinapses
/
Tirosina
/
Proteínas Proto-Oncogênicas c-abl
/
Peptídeos e Proteínas de Sinalização Intracelular
/
Proteínas de Membrana
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article