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Las vasohibinas codifican la actividad obligosinante de la tubulina

Joppe Nieuwenhuis1, Athanassios Adamopoulos1, Onno B Bleijerveld1

  • 1Division of Biochemistry, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands.

Science (New York, N.Y.)
|November 18, 2017
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Resumen

Los investigadores identificaron las vasohibinas como las enzimas buscadas durante mucho tiempo responsables de la obligacinación de la tubulina, una modificación post-traducional clave que afecta la heterogeneidad de los microtúbulos. Este descubrimiento arroja luz sobre el ciclo de tirosinación de la tubulina.

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Área de la Ciencia:

  • Biología celular
  • Biología molecular
  • La bioquímica

Sus antecedentes:

  • Los microtúbulos son polímeros dinámicos esenciales para las funciones celulares.
  • La tubulina sufre modificaciones posttranslacionales, incluida la obligosinación de la alfa-tubulina, que genera heterogeneidad de microtúbulos.
  • Las enzimas que catalizan la obligacinación de la tubulina han permanecido sin identificar durante décadas.

Objetivo del estudio:

  • Para identificar las enzimas evasivas responsables de la obligacionalización de la tubulina.
  • Elucidar los mecanismos moleculares que regulan el ciclo de tirosinación de la tubulina.

Principales métodos:

  • Examen genético en células haploides humanas para identificar los reguladores de la obligacinación de la tubulina.
  • Pruebas bioquímicas con vasohibinas purificadas.
  • Análisis de la función de la vasohibina (VASH1 y VASH2) y de la SVBP.

Principales resultados:

  • El péptido SVBP regula la abundancia de las vasohibinas (VASH1 y VASH2).
  • Las vasohibinas, pero no la SVBP sola, aumentaron significativamente la obligacionalización de la alfa-tubulina.
  • Las vasohibinas purificadas eliminan directamente la tirosina del extremo C de la alfa-tubulina.
  • Las vasohibinas presentan funciones dependientes del tipo de célula en la obligacionalización, con actividad adicional de obligacionalización presente en las células.

Conclusiones:

  • Las vasohibinas son el eslabón perdido en el ciclo de tirosinación de la tubulina, actuando como las enzimas obligosinas primarias.
  • Este hallazgo redefine las funciones conocidas de las vasohibinas más allá de la regulación de la angiogénesis.
  • Comprender la obligosinación de la tubulina es crucial para comprender la dinámica de los microtúbulos y los procesos celulares.