Essential requirement for two-pore channel 1 in NAADP-mediated calcium signaling

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a widespread and potent calcium-mobilizing messenger that is highly unusual in activating calcium channels located on acidic stores. However, the molecular identity of the target protein is unclear. In this study, we show that the previously u...

Descripción completa

Detalles Bibliográficos
Autores principales: Brailoiu, Eugen, Churamani, Dev, Cai, Xinjiang, Schrlau, Michael G., Brailoiu, G. Cristina, Gao, Xin, Hooper, Robert, Boulware, Michael J., Dun, Nae J., Marchant, Jonathan S., Patel, Sandip
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717647/
https://www.ncbi.nlm.nih.gov/pubmed/19620632
http://dx.doi.org/10.1083/jcb.200904073
Descripción
Sumario:Nicotinic acid adenine dinucleotide phosphate (NAADP) is a widespread and potent calcium-mobilizing messenger that is highly unusual in activating calcium channels located on acidic stores. However, the molecular identity of the target protein is unclear. In this study, we show that the previously uncharacterized human two-pore channels (TPC1 and TPC2) are endolysosomal proteins, that NAADP-mediated calcium signals are enhanced by overexpression of TPC1 and attenuated after knockdown of TPC1, and that mutation of a single highly conserved residue within a putative pore region abrogated calcium release by NAADP. Thus, TPC1 is critical for NAADP action and is likely the long sought after target channel for NAADP.

Ejemplares similares