Nesprin-1alpha contributes to the targeting of mAKAP to the cardiac myocyte nuclear envelope.
Exp Cell Res
; 303(2): 388-99, 2005 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-15652351
ABSTRACT
Muscle A-kinase anchoring protein (mAKAP) is a scaffold protein found principally at the nuclear envelope of striated myocytes. mAKAP maintains a complex consisting of multiple signal transduction molecules including the cAMP-dependent protein kinase A, the ryanodine receptor calcium release channel, phosphodiesterase type 4D3, and protein phosphatase 2A. By an unknown mechanism, a domain containing spectrin repeats is responsible for targeting mAKAP to the nuclear envelope. We now demonstrate that the integral membrane protein nesprin-1alpha serves as a receptor for mAKAP on the nuclear envelope in cardiac myocytes. Nesprin-1alpha is inserted into the nuclear envelope by a conserved, C-terminal, klarsicht-related transmembrane domain and forms homodimers by the binding of an amino-terminal spectrin repeat domain. Through the direct binding of the nesprin-1alpha amino-terminal dimerization domain to the third mAKAP spectrin repeat, nesprin-1alpha targets mAKAP to the nuclear envelope. In turn, overexpression of these spectrin repeat domains in myocytes can displace mAKAP from nesprin-1alpha.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Miócitos Cardíacos
/
Proteínas Adaptadoras de Transdução de Sinal
/
Proteínas do Tecido Nervoso
/
Membrana Nuclear
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos