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Los canales Ca(V) 1 y Ca(V) 2 activan modos distintos de señalización de Ca(2+) para controlar la expresión génica

Damian G Wheeler¹, Rachel D Groth, Huan Ma

¹Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305-5345, USA.

|May 29, 2012

Resumen

Los diferentes tipos de canales de calcio (Ca(V) 1 y Ca(V) 2) regulan claramente la expresión génica neuronal para el aprendizaje y la memoria. Los canales Ca(V) 1 conducen eficientemente la señalización nuclear, mientras que los canales Ca(V) 2 son menos efectivos debido al búfer espacial.

Área de la Ciencia:

La neurociencia es la neurociencia.
Biología Molecular Biología Molecular
La señalización celular.

Sus antecedentes:

La expresión génica dependiente de la actividad en las neuronas es crucial para las funciones cognitivas como el aprendizaje y la memoria.
Las funciones precisas de fuentes distintas de calcio (Ca2+) en la señalización neuronal siguen sin estar claras.

Objetivo del estudio:

Para investigar si los diferentes tipos de canales de calcio (Ca (V) 1 y Ca (V) 2) señalan de manera distinta o contribuyen a un conjunto común de calcio.
Para dilucidar los mecanismos por los cuales estos canales influyen en la fosforilación CREB y la expresión génica.

Principales métodos:

Grabaciones electrofisiológicas para analizar las propiedades de bloqueo de canales.
Imágenes de calcio para evaluar la dinámica espacial y temporal de las señales de Ca2+.
Análisis bioquímicos para medir la agregación de CaMKII y la fosforilación de CREB.

Principales resultados:

Ambos canales Ca(V) 1 y Ca(V) 2 acoplan la despolarización a la fosforilación CREB y la expresión génica, pero a través de mecanismos distintos.
Los canales Ca(V) 1 utilizan el nanodominio Ca2+ para la activación localizada de CaMKII y la señalización nuclear.
Los canales de Ca (V) 2 requieren una elevación más amplia de Ca2+ y son menos eficientes debido al amortiguamiento espacial por parte de los orgánulos intracelulares.

Conclusiones:

Los distintos modos de señalización espacial de los canales Ca(V) 1 y Ca(V) 2 tienen un impacto diferencial en la expresión génica neuronal.
Los canales Ca(V) 1 son más efectivos para impulsar la expresión génica dependiente de la actividad, esencial para el aprendizaje y la memoria.
El amortiguamiento del calcio sesgado por la fuente influye significativamente en la eficacia de las vías de señalización neuronal.

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