Src-mediated phosphorylation of ßPix-b regulates dendritic spine morphogenesis.
J Cell Sci
; 132(5)2019 02 25.
Article
en En
| MEDLINE
| ID: mdl-30683798
ABSTRACT
PAK-interacting guanine nucleotide exchange factor (ßPix; also known as Arhgef7) has been implicated in many actin-based cellular processes, including spine morphogenesis in neurons. However, the molecular mechanisms by which ßPix controls spine morphology remain elusive. Previously, we have reported the expression of several alternative spliced ßPix isoforms in the brain. Here, we report a novel finding that the b isoform of ßPix (ßPix-b) mediates the regulation of spine and synapse formation. We found that ßPix-b, which is mainly expressed in neurons, enhances spine and synapse formation through preferential localization at spines. In neurons, glutamate treatment efficiently stimulates Rac1 GEF activity of ßPix-b. The glutamate stimulation also promotes Src-mediated phosphorylation of ßPix-b in both an AMPA receptor- and NMDA receptor-dependent manner. Tyrosine 598 (Y598) of ßPix-b is identified as the major Src-mediated phosphorylation site. Finally, Y598 phosphorylation of ßPix-b enhances its Rac1 GEF activity that is critical for spine and synapse formation. In conclusion, we provide a novel mechanism by which ßPix-b regulates activity-dependent spinogenesis and synaptogenesis via Src-mediated phosphorylation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transmisión Sináptica
/
Espinas Dendríticas
/
Factores de Intercambio de Guanina Nucleótido Rho
/
Neuronas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Cell Sci
Año:
2019
Tipo del documento:
Article