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Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
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Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
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TMCO1 es un canal de Ca2+ activado por carga

Qiao-Chu Wang1, Qiaoxia Zheng1, Haiyan Tan2

  • 1State Key Laboratory of Membrane Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100101, China.

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|May 24, 2016
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Resumen

La proteína TMCO1 del retículo endoplasmático (ER) actúa como un canal de calcio activado por la carga de calcio (CLAC), evitando que las reservas de calcio ER se sobrellenen. Este descubrimiento ofrece información sobre la homeostasis del calcio celular y los trastornos del desarrollo relacionados.

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Área de la Ciencia:

  • Biología celular
  • Biología molecular
  • La biofísica

Sus antecedentes:

  • El mantenimiento de la homeostasis del calcio (Ca2+) en el retículo endoplasmático (ER) es vital para la señalización y la función celular.
  • El canal de Ca2+ activado por liberación de Ca2+ (CRAC) rellena las reservas de ER, pero se desconocen los mecanismos que evitan la sobrecarga de ER Ca2+.

Objetivo del estudio:

  • Investigar el papel de TMCO1 en la regulación de los niveles de ER Ca2+.
  • Caracterizar el TMCO1 como un canal potencial de Ca2+ implicado en la prevención de la sobrecarga de Ca2+ en el ER.

Principales métodos:

  • Estudió la función de TMCO1 en la regulación de ER Ca2+.
  • Se investigó el estado de oligomerización de TMCO1 en respuesta a los niveles de Ca2+.
  • Actividad del canal TMCO1 reconstituido en liposomas gigantes.
  • Se examinó la función de TMCO1 en modelos de ratón nocaut.

Principales resultados:

  • TMCO1 es una proteína transmembrana de ER que evita que las reservas de Ca2+ de ER se sobrellen.
  • TMCO1 funciona como un canal de Ca2+ activado por carga (CLAC).
  • TMCO1 se somete a una tetramerización reversible al sobrecargarse con ER Ca2+ y se desmonta al agotarse.
  • Los ratones con knockout TMCO1 muestran mal manejo de ER Ca2+ y características del espectro de displasia cerebrofaciotorácica.

Conclusiones:

  • TMCO1 actúa como un mecanismo de protección crucial contra el exceso de llenado de ER Ca2+.
  • La disfunción de TMCO1 está relacionada con los trastornos del espectro de la displasia cerebrofaciotorácica.
  • TMCO1 representa un nuevo objetivo para la comprensión y el tratamiento de los trastornos de desregulación de Ca2+.