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NAADP moviliza el calcio de los orgánulos ácidos a través de canales de dos poros
Peter J Calcraft1, Margarida Ruas, Zui Pan
1Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, University of Edinburgh, Hugh Robson Building, Edinburgh EH8 9XD, Scotland, UK.
Nature
|April 24, 2009
Resumen
Los canales de dos poros (TPC) se identifican como receptores de fosfato de adenina dinucleótido de ácido nicotínico (NAADP). Estos TPC liberan calcio de los orgánulos ácidos, lo que influye en las vías de señalización de calcio celular más amplias.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- Fisiología Fisiología Fisiología.
Sus antecedentes:
- La movilización de calcio (Ca2+) de las reservas intracelulares es crucial para la señalización celular.
- El inositol-1,4,5-trisfosfato (InsP3) y la ribosa ADP cíclica regulan la liberación de Ca2+ a través de las InsP3R y las RyR.
- Los objetivos y los receptores para la NAADP siguen siendo objeto de debate, aunque los compartimentos relacionados con los lisosomas están implicados.
Objetivo del estudio:
- Para identificar la identidad molecular de los receptores NAADP.
- Para aclarar el papel de los TPC en la señalización de Ca2+ mediada por NAADP.
- Comprender la contribución de las TPC a la regulación celular del Ca2+.
Principales métodos:
- Expresión de TPC1, TPC2 humano y TPC3 de pollo en células HEK293.
- Evaluación de la afinidad de unión de NAADP a las membranas enriquecidas con TPC2.
- Investigación de la liberación de Ca2+ inducida por NAADP bajo diversas condiciones, incluida la interrupción del gradiente de protones lisosomal y la ablación de TPC2.
Principales resultados:
- Las TPC (TPC1, TPC2, TPC3) están localizadas en las membranas endosomales y lisosomales.
- TPC2 exhibe la unión de NAADP de alta afinidad y media la liberación de Ca2+ inducida por NAADP de las reservas relacionadas con los lisosomas.
- La liberación de Ca2+ inducida por NAADP depende del gradiente de protones lisosomal y la expresión de TPC2, y puede amplificar las señales de Ca2+ a través de InsP3Rs.
Conclusiones:
- Las TPC funcionan como receptores NAADP, liberando Ca2+ de los orgánulos ácidos.
- Esta liberación de Ca2+ puede iniciar eventos de señalización secundarios a través del retículo sarcoplasmático / endoplasmático.
- Los TPC ofrecen nuevos conocimientos sobre la regulación y organización de la señalización celular de Ca2+ y las funciones fisiológicas de la NAADP.
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