Regulation of N-cadherin-mediated adhesion by the p35-Cdk5 kinase.
Curr Biol
; 10(7): 363-72, 2000 Apr 06.
Article
em En
| MEDLINE
| ID: mdl-10753743
ABSTRACT
BACKGROUND:
The p35-Cdk5 kinase has been implicated in a variety of functions in the central nervous system (CNS), including axon outgrowth, axon guidance, fasciculation, and neuronal migration during cortical development. In p35(-/-) mice, embryonic cortical neurons are unable to migrate past their predecessors, leading to an inversion of cortical layers in the adult cortex.RESULTS:
In order to identify molecules important for p35-Cdk5-dependent function in the cortex, we screened for p35-interacting proteins using the two-hybrid system. In this study, we report the identification of a novel interaction between p35 and the versatile cell adhesion signaling molecule beta-catenin. The p35 and beta-catenin proteins interacted in vitro and colocalized in transfected COS cells. In addition, the p35-Cdk5 kinase was associated with a beta-catenin-N-cadherin complex in the cortex. In N-cadherin-mediated aggregation assays, inhibition of Cdk5 kinase activity using the Cdk5 inhibitor roscovitine led to the formation of larger aggregates of embryonic cortical neurons. This finding was recapitulated in p35(-/-) cortical neurons, which aggregated to a greater degree than wild-type neurons. In addition, introduction of active p35-Cdk5 kinase into COS cells led to a decreased beta-catenin-N-cadherin interaction and loss of cell adhesion.CONCLUSIONS:
The association between p35-Cdk5 and an N-cadherin adhesion complex in cortical neurons and the modulation of N-cadherin-mediated aggregation by p35-Cdk5 suggests that the p35-Cdk5 kinase is involved in the regulation of N-cadherin-mediated adhesion in cortical neurons.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Caderinas
/
Transativadores
/
Córtex Cerebral
/
Quinases Ciclina-Dependentes
/
Proteínas do Citoesqueleto
/
Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Curr Biol
Assunto da revista:
BIOLOGIA
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos