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An NAADP-gated two-pore channel targeted to the plasma membrane uncouples triggering from amplifying Ca2+ signals.

ABSTRACT: Nicotinic acid adenine dinucleotide phosphate (NAADP) is a ubiquitous messenger proposed to stimulate Ca(2+) release from acidic organelles via two-pore channels (TPCs). It has been difficult to resolve this trigger event from its amplification via endoplasmic reticulum Ca(2+) stores, fuelling speculation that archetypal intracellular Ca(2+) channels are the primary targets of NAADP. Here, we redirect TPC2 from lysosomes to the plasma membrane and show that NAADP evokes Ca(2+) influx independent of ryanodine receptors and that it activates a Ca(2+)-permeable channel whose conductance is reduced by mutation of a residue within a putative pore. We therefore uncouple TPC2 from amplification pathways and prove that it is a pore-forming subunit of an NAADP-gated Ca(2+) channel.

SUBMITTER: Brailoiu E

PROVIDER: S-EPMC2992283 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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An NAADP-gated two-pore channel targeted to the plasma membrane uncouples triggering from amplifying Ca2+ signals.

Brailoiu Eugen E Rahman Taufiq T Churamani Dev D Prole David L DL Brailoiu G Cristina GC Hooper Robert R Taylor Colin W CW Patel Sandip S

The Journal of biological chemistry 20100929 49

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a ubiquitous messenger proposed to stimulate Ca(2+) release from acidic organelles via two-pore channels (TPCs). It has been difficult to resolve this trigger event from its amplification via endoplasmic reticulum Ca(2+) stores, fuelling speculation that archetypal intracellular Ca(2+) channels are the primary targets of NAADP. Here, we redirect TPC2 from lysosomes to the plasma membrane and show that NAADP evokes Ca(2+) influx independent ...[more]

PMID: 20880839

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NAADP-evoked Ca2+ signals through two-pore channel-1 require arginine residues in the first S4-S5 linker.

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The HOOK region of voltage-gated Ca2+ channel β subunits senses and transmits PIP2 signals to the gate.

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