Drebrin contains a cryptic F-actin-bundling activity regulated by Cdk5 phosphorylation.
J Cell Biol
; 202(5): 793-806, 2013 Sep 02.
Article
em En
| MEDLINE
| ID: mdl-23979715
ABSTRACT
Drebrin is an actin filament (F-actin)-binding protein with crucial roles in neuritogenesis and synaptic plasticity. Drebrin couples dynamic microtubules to F-actin in growth cone filopodia via binding to the microtubule-binding +TIP protein EB3 and organizes F-actin in dendritic spines. Precisely how drebrin interacts with F-actin and how this is regulated is unknown. We used cellular and in vitro assays with a library of drebrin deletion constructs to map F-actin binding sites. We discovered two domains in the N-terminal half of drebrin-a coiled-coil domain and a helical domain-that independently bound to F-actin and cooperatively bundled F-actin. However, this activity was repressed by an intramolecular interaction relieved by Cdk5 phosphorylation of serine 142 located in the coiled-coil domain. Phospho-mimetic and phospho-dead mutants of serine 142 interfered with neuritogenesis and coupling of microtubules to F-actin in growth cone filopodia. These findings show that drebrin contains a cryptic F-actin-bundling activity regulated by phosphorylation and provide a mechanistic model for microtubule-F-actin coupling.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neuropeptídeos
/
Actinas
/
Quinase 5 Dependente de Ciclina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2013
Tipo de documento:
Article