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La segregación apical mediada por PTEN de fosfoinosítidos controla la morfogénesis epitelial a través de Cdc42
Fernando Martin-Belmonte1, Ama Gassama, Anirban Datta
1Department of Anatomy, University of California, San Francisco, CA 94143, USA. fernando.martin-belmonte@ucsf.edu
Cell
|January 27, 2007
Resumen
PTEN, fosfatidilinositol 4,5-bisfosfato (PtdIns(4,5) P2), Annexin 2 (Anx2), Cdc42 y la proteína kinasa C atípica (aPKC) son cruciales para la formación de la superficie apical y el lumen en los órganos epiteliales. Su acción coordinada asegura el correcto desarrollo epitelial.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología del desarrollo Biología del desarrollo.
- La bioquímica es la bioquímica.
Sus antecedentes:
- El desarrollo de los órganos epiteliales se basa en la formación de superficies apicales y lúmenes, un proceso que no se comprende completamente.
- La membrana plasmática apical es crítica para la función epitelial y la organización del tejido.
Objetivo del estudio:
- Para dilucidar los mecanismos moleculares que controlan la membrana plasmática apical y la formación de lumen durante la morfogénesis epitelial.
- Para investigar el papel del PTEN y el fosfatidilinositol 4,5-bisfosfato (PtdIns(4,5) P2) en el establecimiento del dominio apical.
Principales métodos:
- Se utilizaron modelos tridimensionales de cultivo celular para observar el desarrollo de quistes epiteliales.
- Investigó la localización de proteínas e interacciones utilizando pruebas de inmunofluorescencia y bioquímicas.
- Realizó estudios de pérdida de función para proteínas clave, incluidas PTEN, Annexin 2 (Anx2), Cdc42 y kinasa proteica atípica C (aPKC).
Principales resultados:
- El PTEN se localiza en la membrana plasmática apical, mediando el enriquecimiento de PtdIns ((4,5) P2 durante el desarrollo del quiste.
- El PtdIns ((4,5) P2 ectópico en la superficie basolateral conduce a la mala localización de la proteína apical.
- Anx2 se une a PtdIns(4,5) P2 y recluta Cdc42, que a su vez recluta aPKC a la superficie apical.
Conclusiones:
- PTEN, PtdIns{4,5) P2, Anx2, Cdc42 y aPKC forman una vía crítica para la formación de la membrana plasmática apical y la luz.
- La interrupción de esta vía afecta el desarrollo normal de los órganos epiteliales.
- Este estudio revela un nuevo mecanismo que controla el establecimiento del dominio apical en los tejidos epiteliales.
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