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PRICKLE3 protege las proteínas VANGL de la fosforilación mediada por CK1 y la degradación mediada por RNF43
Katarzyna A Radaszkiewicz1, Tomasz W Radaszkiewicz1, Pavla Kolářová1
1Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czechia.
Communications biology
|December 27, 2025
Resumen
PRICKLE3 es un regulador clave de la señalización WNT/polaridad celular planar (PCP). Estabiliza las proteínas VANGL1/2 al prevenir la fosforilación, crucial para la polaridad celular y el desarrollo de tejidos.
Área de la Ciencia:
- Biología Celular
- Biología del Desarrollo
- Biología Molecular
Sus antecedentes:
- La vía WNT/polaridad celular planar (PCP) es vital para el desarrollo de los vertebrados, controlando la polaridad celular y la organización de tejidos.
- Las funciones individuales de las proteínas PRICKLE dentro de la vía WNT/PCP no se han dilucidado completamente.
- La comprensión de los mecanismos de las proteínas PRICKLE es crucial para comprender los procesos de desarrollo y las enfermedades.
Objetivo del estudio:
- Identificar y caracterizar el papel de PRICKLE3 en la señalización WNT/PCP.
- Elucidar los mecanismos moleculares por los cuales PRICKLE3 regula los componentes de WNT/PCP.
- Proporcionar herramientas moleculares novedosas para estudiar la familia de proteínas PRICKLE.
Principales métodos:
- Biotinilación por proximidad mejorada (miniTurboID) acoplada a espectrometría de masas para identificar interacciones proteicas.
- Inmunotransferencia e imagen en vivo para evaluar la estabilidad y localización de proteínas.
- Ensayos funcionales en células humanas, Xenopus laevis y embriones de pez cebra (Danio rerio).
Principales resultados:
- PRICKLE3 se identificó como un regulador central de la señalización WNT/PCP en diferentes especies.
- PRICKLE3 se asocia con VANGL1 y VANGL2 en la membrana plasmática.
- PRICKLE3 estabiliza selectivamente VANGL1/2 inhibiendo la fosforilación mediada por Caseína quinasa 1ε (CK1ε) y modulando la actividad de RNF43.
- PRICKLE1 no mostró efectos estabilizadores similares en las proteínas VANGL.
Conclusiones:
- PRICKLE3 emplea un mecanismo único para estabilizar los complejos VANGL inhibiendo CK1ε y suprimiendo RNF43.
- Esta función específica de PRICKLE3 es crítica para la regulación de la vía WNT/PCP, impactando la polaridad celular y la arquitectura tisular.
- El estudio proporciona un interactoma detallado y herramientas valiosas para la investigación futura de las proteínas PRICKLE en el desarrollo y las enfermedades.
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