Disruption of cytoskeletal integrity impairs Gi-mediated signaling due to displacement of Gi proteins.
J Cell Biol
; 154(4): 753-61, 2001 Aug 20.
Article
em En
| MEDLINE
| ID: mdl-11514589
ABSTRACT
beta1 integrins play a crucial role as cytoskeletal anchorage proteins. In this study, the coupling of the cytoskeleton and intracellular signaling pathways was investigated in beta1 integrin deficient (-/-) embryonic stem cells. Muscarinic inhibition of the L-type Ca2+ current (ICa) and activation of the acetylcholine-activated K+ current (IK,ACh) was found to be absent in beta1 integrin-/- cardiomyocytes. Conversely, beta adrenoceptor-mediated modulation of ICa was unaffected by the absence of beta1 integrins. This defect in muscarinic signaling was due to defective G protein coupling. This was supported by deconvolution microscopy, which demonstrated that Gi exhibited an atypical subcellular distribution in the beta1 integrin-/- cardiomyocytes. A critical role of the cytoskeleton was further demonstrated using cytochalasin D, which displaced Gi and impaired muscarinic signaling. We conclude that cytoskeletal integrity is required for correct localization and function of Gi-associated signaling microdomains.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Citoesqueleto
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Receptores Adrenérgicos beta
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Receptores Muscarínicos
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Integrina beta1
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Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP
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Miocárdio
Limite:
Animals
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Alemanha