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Señalización ERLIN2-Ca²⁺-CREB coordina el tiempo circadiano a través de la retroalimentación CRY1/CRY2

Yuwen Chen¹, Jiaxin Lin^1,2, Zongyou Zou¹

¹Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

|January 23, 2026

Resumen

La proteína 2 asociada a las balsas de lípidos del retículo endoplásmico (ERLIN2) regula los ritmos circadianos periféricos controlando la liberación de calcio (Ca2+) y activando la vía CREB. Este descubrimiento revela un nuevo eje ERLIN2-Ca2+-CREB-CRY1/2 crucial para el control del reloj celular.

Área de la Ciencia:

Biología Celular
Cronobiología
Biología Molecular

Sus antecedentes:

La regulación del reloj circadiano periférico es esencial para la función celular.
La dinámica del calcio (Ca2+) está implicada en los ritmos circadianos, pero los reguladores río arriba son desconocidos.

Objetivo del estudio:

Identificar nuevos reguladores del reloj circadiano periférico.
Elucidar los mecanismos moleculares que vinculan la señalización del calcio con la ritmicidad circadiana.

Principales métodos:

Reducción y sobreexpresión de ERLIN2 en células de músculo esquelético C2C12.
Medición de transitorios de Ca2+ utilizando activadores e inhibidores de IP3R.
Análisis de la fosforilación de CREB y la transcripción de CRY1/2.
Investigación de la vía de señalización CaMKII-MAPK-CREB.

Principales resultados:

ERLIN2 regula positivamente la transcripción de CRY1/2 y mantiene la ritmicidad circadiana.
ERLIN2 controla la liberación de Ca2+ mediada por IP3R y activa la vía CaMKII-MAPK-CREB.
Los transitorios de Ca2+ inducidos por ATP, la fosforilación de CREB y la expresión de Per1 se bloquean por inhibición de IP3R, Ca2+ o CaMKII.
CRY1 mejora y CRY2 suprime la señalización de CREB, formando un bucle de retroalimentación con ERLIN2.

Conclusiones:

ERLIN2 es un regulador clave que vincula la señalización del calcio con los relojes circadianos periféricos.
El eje ERLIN2-Ca2+-CREB-CRY1/2 acopla los sitios de contacto de membrana con la regulación circadiana.
Este estudio proporciona nuevas perspectivas sobre los mecanismos río arriba que controlan la función del reloj celular.

Palabras clave:

Vía CREB Retroalimentación CRY1/CRY2 ERLIN2 Señalización de calcio Ritmo circadiano

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