The cell polarity protein mInsc regulates neutrophil chemotaxis via a noncanonical G protein signaling pathway.
Dev Cell
; 26(3): 292-302, 2013 Aug 12.
Article
em En
| MEDLINE
| ID: mdl-23891662
ABSTRACT
Successful chemotaxis requires not only increased motility but also sustained directionality. Here, we show that, during neutrophil chemotaxis via receptors coupled with the Gi family of heterotrimeric G proteins, directional movement is regulated by mInsc, a mammalian protein distantly related to the Drosophila polarity-organizer Inscuteable. The GDP-bound, Gßγ-free Gαi subunit accumulates at the front of chemotaxing neutrophils to recruit mInsc-complexed with the Par3-aPKC evolutionarily conserved polarity complex-via LGN/AGS3 that simultaneously binds to Gαi-GDP and mInsc. Both mInsc-deficient and aPKC-blocked neutrophils exhibit a normal motile activity but migrate in an undirected manner. mInsc deficiency prevents neutrophils from efficiently stabilizing pseudopods at the leading edge; the stability is restored by wild-type mInsc, but not by a mutant protein defective in binding to LGN/AGS3. Thus, mInsc controls directional migration via noncanonical G protein signaling, in which Gßγ-free Gαi-GDP, a product from Gαi-GTP released after receptor activation, plays a central role.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Fatores Quimiotáticos
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Polaridade Celular
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Proteínas de Ciclo Celular
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Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP
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Neutrófilos
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article