A kindlin-3-leupaxin-paxillin signaling pathway regulates podosome stability.
J Cell Biol
; 218(10): 3436-3454, 2019 10 07.
Article
em En
| MEDLINE
| ID: mdl-31537712
ABSTRACT
Binding of kindlins to integrins is required for integrin activation, stable ligand binding, and subsequent intracellular signaling. How hematopoietic kindlin-3 contributes to the assembly and stability of the adhesion complex is not known. Here we report that kindlin-3 recruits leupaxin into podosomes and thereby regulates paxillin phosphorylation and podosome turnover. We demonstrate that the activity of the protein tyrosine phosphatase PTP-PEST, which controls paxillin phosphorylation, requires leupaxin. In contrast, despite sharing the same binding mode with leupaxin, paxillin recruitment into podosomes is kindlin-3 independent. Instead, we found paxillin together with talin and vinculin in initial adhesion patches of kindlin-3-null cells. Surprisingly, despite its presence in these early adhesion patches, podosomes can form in the absence of paxillin or any paxillin member. In conclusion, our findings show that kindlin-3 not only activates and clusters integrins into podosomes but also regulates their lifetime by recruiting leupaxin, which controls PTP-PEST activity and thereby paxillin phosphorylation and downstream signaling.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Transdução de Sinais
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Moléculas de Adesão Celular
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Proteínas do Citoesqueleto
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Paxilina
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Podossomos
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article