Integrin α3ß1 regulates kidney collecting duct development via TRAF6-dependent K63-linked polyubiquitination of Akt.
Mol Biol Cell
; 26(10): 1857-74, 2015 May 15.
Article
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| MEDLINE
| ID: mdl-25808491
ABSTRACT
The collecting system of the kidney develops from the ureteric bud (UB), which undergoes branching morphogenesis, a process regulated by multiple factors, including integrin-extracellular matrix interactions. The laminin (LM)-binding integrin α3ß1 is crucial for this developmental program; however, the LM types and LM/integrin α3ß1-dependent signaling pathways are poorly defined. We show that α3 chain-containing LMs promote normal UB branching morphogenesis and that LM-332 is a better substrate than LM-511 for stimulating integrin α3ß1-dependent collecting duct cell functions. We demonstrate that integrin α3ß1-mediated cell adhesion to LM-332 modulates Akt activation in the developing collecting system and that Akt activation is PI3K independent but requires decreased PTEN activity and K63-linked polyubiquitination. We identified the ubiquitin-modifying enzyme TRAF6 as an interactor with the integrin ß1 subunit and regulator of integrin α3ß1-dependent Akt activation. Finally, we established that the developmental defects of TRAF6- and integrin α3-null mouse kidneys are similar. Thus K63-linked polyubiquitination plays a previously unrecognized role in integrin α3ß1-dependent cell signaling required for UB development and may represent a novel mechanism whereby integrins regulate signaling pathways.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Integrina alfa3beta1
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Factor 6 Asociado a Receptor de TNF
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Proteínas Proto-Oncogénicas c-akt
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Túbulos Renales Colectores
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Morfogénesis
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Mol Biol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2015
Tipo del documento:
Article