The acid test: the discovery of two-pore channels (TPCs) as NAADP-gated endolysosomal Ca(2+) release channels.
In this review, we describe the background and implications of our recent discovery that two-pore channels (TPCs) comprise a novel class of calcium release channels gated by the intracellular messenger nicotinic acid adenine dinucleotide phosphate (NAADP). Their localisation to the endolysosomal system highlights a new function for these organelles as targets for NAADP-mediated Ca(2+) mobilisation. In addition, we describe how TPCs may also trigger further Ca(2+) release by coupling to the endoplasmic reticular stores through activation of IP(3) receptors and ryanodine receptors.
Galione
Antony
A
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK. antony.galione@pharm.ox.ac.uk
Evans
A Mark
AM
Ma
Jianjie
J
Parrington
John
J
Arredouani
Abdelilah
A
Cheng
Xiaotong
X
Zhu
Michael X
MX
D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D011992:Endosomes / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008247:Lysosomes / Q000502:physiology*; D008958:Models, Molecular; D009249:NADP / Q000031:analogs & derivatives* / Q000502:physiology; D010802:Phylogeny
D015220:Calcium Channels; D009249:NADP; C024376:NAADP