Dual lipidation of the brain-specific Cdc42 isoform regulates its functional properties.
Biochem J
; 456(3): 311-22, 2013 Dec 15.
Article
en En
| MEDLINE
| ID: mdl-24059268
ABSTRACT
Cdc42 (cell division cycle 42) is a member of the Rho GTPase family which regulates a variety of cellular activities by controlling actin cytoskeleton and gene expression. Cdc42 is expressed in the form of two splice variants. The canonical Cdc42 isoform is prenylated (Cdc42-prenyl), whereas the brainspecific isoform can be palmitoylated (Cdc42-palm). In the present study we have demonstrated palmitoylation of endogenous Cdc42 in rodent and human brains and identified Cys(188) and Cys(189) as acylation sites of Cdc42-palm. Moreover, we have shown that Cys(188) can also be prenylated. Analysis of acylation-deficient mutants revealed that lipidation of Cys(188) is essential for proper membrane binding of Cdc42-palm as well as for Cdc42-mediated regulation of gene transcription and induction of densely packed filopodia in neuroblastoma cells. We also found that Cdc42-prenyl is a dominant splice variant in a wide range of commonly used cell lines as well as in the cerebellum, whereas Cdc42-palm is the main Cdc42 isoform in hippocampus, where it is critically involved in the formation of dendritic filopodia and spines. Replacement of endogenous Cdc42 by its acylation-deficient mutants revealed the importance of Cdc42-palm lipidation for its morphogenic and synaptogenic effects in neurons. These findings demonstrate that dual lipidation of Cdc42-palm represents an important regulator of morphogenic signalling in hippocampal neurons.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cerebelo
/
Proteína de Unión al GTP cdc42
/
Dendritas
/
Lipoilación
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Hipocampo
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem J
Año:
2013
Tipo del documento:
Article
País de afiliación:
Alemania