Rap1 controls activation of the α(M)ß(2) integrin in a talin-dependent manner.
J Cell Biochem
; 111(4): 999-1009, 2010 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-20665668
ABSTRACT
The small GTPase Rap1 and the cytoskeletal protein talin regulate binding of C3bi-opsonised red blood cells (RBC) to integrin α(M)ß(2) in phagocytic cells, although the mechanism has not been investigated. Using COS-7 cells transfected with α(M)ß(2), we show that Rap1 acts on the ß(2) and not the α(M) chain, and that residues 732-761 of the ß(2) subunit are essential for Rap1-induced RBC binding. Activation of α(M)ß(2) by Rap1 was dependent on W747 and F754 in the ß(2) tails, which are required for talin head binding, suggesting a link between Rap1 and talin in this process. Using talin1 knock-out cells or siRNA-mediated talin1 knockdown in the THP-1 monocytic cell line, we show that Rap1 acts upstream of talin but surprisingly, RIAM knockdown had little effect on integrin-mediated RBC binding or cell spreading. Interestingly, Rap1 and talin influence each other's localisation at phagocytic cups, and co-immunoprecipitation experiments suggest that they interact together. These results show that Rap1-mediated activation of α(M)ß(2) in macrophages shares both common and distinct features from Rap1 activation of α(IIb)ß(3) expressed in CHO cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antígeno de Macrófago 1
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Talina
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Proteínas rap1 de Ligação ao GTP
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Cell Biochem
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Reino Unido