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El antagonismo estocástico entre dos proteínas gobierna un interruptor de destino celular bacteriano

Nathan D Lord¹, Thomas M Norman^1,2, Ruoshi Yuan¹

¹Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.

Science (New York, N.Y.)

|October 12, 2019

Resumen

Las decisiones sobre el destino celular en Bacillus subtilis surgen de una simple competencia entre dos proteínas, no de circuitos de retroalimentación complejos. Este mecanismo estocástico asegura estados celulares y herencia distintos y estables.

Área de la Ciencia:

Microbiología
Biología de sistemas
Biología molecular

Sus antecedentes:

Las decisiones sobre el destino celular requieren variabilidad para diversos tipos de células.
Los modelos tradicionales proponen redes reguladoras complejas con bucles de retroalimentación para estados celulares estables.
Comprender las bases moleculares de la diferenciación celular es crucial.

Objetivo del estudio:

Investigar los mecanismos moleculares subyacentes al cambio de destino celular en el Bacillus subtilis.
Desafiar el punto de vista prevaleciente de los circuitos de retroalimentación complejos en la determinación del destino celular.
Explorar modelos alternativos para lograr estados celulares discretos y estables.

Principales métodos:

Utilizó mutaciones reguladoras de Bacillus subtilis.
Se han empleado experimentos de reconstitución in vivo.
Marco teórico aplicado para los procesos estocásticos.

Principales resultados:

Demostró que el cambio de destino celular puede explicarse por la competencia estocástica entre dos proteínas producidas constitutivamente.
Se demostró que esta simple interacción antagónica subyace a los estados celulares discretos, la herencia multigeneracional y el momento del compromiso.
Se ha identificado un nuevo mecanismo para la determinación del destino celular en Bacillus subtilis.

Conclusiones:

La simple competencia estocástica entre proteínas antagónicas puede impulsar las decisiones del destino celular.
Este mecanismo proporciona una explicación parsimoniosa para las características clave del cambio de destino celular.
Las interacciones proteicas antagónicas pueden ser un mecanismo ampliamente aplicable para la determinación del destino celular en varios organismos.

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