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Function and dysfunction of two-pore channels
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DOI：10.1126/scisignal.aab3314.png)
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Abstract
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Two-pore channels (TPCs) are evolutionarily important members of the voltage-gated ion channel superfamily. TPCs localize to acidic Ca2+ stores within the endolysosomal system. Most evidence indicate that TPCs mediate Ca2+ signals through the Ca2+-mobilizing messenger nicotinic acid adenine dinucleotide phosphate (NAADP) to control a range of Ca2+-dependent events. Recent studies clarify the mechanism of TPC activation and identify roles for TPCs in disease, highlighting the regulation of endolysosomal membrane traffic by local Ca2+ fluxes. Chemical targeting of TPCs to maintain endolysosomal well-being may be beneficial in disorders as diverse as Parkinson's disease, fatty liver disease, and Ebola virus infection.
Keywords:
ADENINE-DINUCLEOTIDE PHOSPHATE
VOLTAGE-GATED SODIUM
ION-CHANNEL
MOBILIZES CALCIUM
RELEASE CHANNEL
TPC PROTEINS
NAADP
CA2+
ISOFORMS
DISEASE
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