TY - JOUR
T1 - Essential requirement for two-pore channel 1 in NAADP-mediated calcium signaling
AU - Brailoiu, Eugen
AU - Churamani, Dev
AU - Cai, Xinjiang
AU - Schrlau, Michael G.
AU - Brailoiu, G. Cristina
AU - Gao, Xin
AU - Hooper, Robert
AU - Boulware, Michael J.
AU - Dun, Nae J.
AU - Marchant, Jonathan S.
AU - Patel, Sandip
PY - 2009/7/27
Y1 - 2009/7/27
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.200904073
DO - 10.1083/jcb.200904073
M3 - Article
C2 - 19620632
AN - SCOPUS:67749143745
SN - 0021-9525
VL - 186
SP - 201
EP - 209
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 2
ER -