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La escisión mediada por caspase de la flipasa fosfolípida para la exposición apoptótica a la fosfatidilserina

Katsumori Segawa¹, Sachiko Kurata¹, Yuichi Yanagihashi¹

¹Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Kyoto 606-8501, Japan.

Science (New York, N.Y.)

|June 7, 2014

Resumen

Un estudio identificó ATP11C y CDC50A como cruciales para la asimetría de fosfolípidos en las membranas celulares. La inactivación de su actividad de la flipasa durante la apoptosis previene la exposición a la fosfatidilserina, bloqueando la envoltura de los macrófagos.

Área de la Ciencia:

Biología celular Biología celular.
La bioquímica es la bioquímica.
Investigación de la investigación de la apoptosis.

Sus antecedentes:

Los fosfolípidos muestran una distribución asimétrica en la membrana plasmática, crucial para la función celular.
Esta asimetría se interrumpe durante la apoptosis, lo que lleva a la exposición a la fosfatidilserina (PtdSer) en la superficie celular.
La exposición a PtdSer sirve como una señal para el aclaramiento celular.

Objetivo del estudio:

Para identificar la maquinaria molecular responsable de mantener la translocación de los aminofosfolípidos.
Para investigar el papel de la actividad de la flipasa en la exposición apoptótica al PtdSer.
Para aclarar el mecanismo por el cual PtdSer actúa como una señal de "cómete a mí".

Principales métodos:

Realizó un examen genético haploide en células humanas para identificar genes involucrados en la translocación de fosfolípidos.
Utilizó la mutagénesis dirigida en el sitio para crear variantes resistentes a la caspasa de ATP11C.
Se evaluó la exposición a PtdSer y la envoltura de macrófagos en células con función manipulada de ATP11C y CDC50A.

Principales resultados:

Identificó ATP11C y CDC50A como esenciales para la translocación de aminofosfolípidos, lo que demuestra la actividad de la flipasa.
Se demostró que la inactivación mediada por caspasa de la actividad de la ATP11C en la flipasa es necesaria para la exposición a PtdSer durante la apoptosis.
Se ha demostrado que el ATP11C resistente a la caspasa previene la exposición al PtdSer y la posterior envoltura de los macrófagos.
Se confirmó que la deficiencia de CDC50A conduce a la exposición superficial de PtdSer y al reconocimiento de macrófagos.

Conclusiones:

ATP11C y CDC50A funcionan como un complejo de flipase, manteniendo la asimetría fosfolípida de la membrana plasmática.
La inactivación de esta actividad de la flipasa durante la apoptosis es un paso crítico para exponer PtdSer.
La fosfatidilserina es una señal de "cómeme" suficiente para la fagocitosis de los macrófagos, independiente de otros marcadores apoptóticos.

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