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Publication : TPC proteins are phosphoinositide- activated sodium-selective ion channels in endosomes and lysosomes.

First Author  Wang X Year  2012
Journal  Cell Volume  151
Issue  2 Pages  372-83
PubMed ID  23063126 Mgi Jnum  J:189070
Mgi Id  MGI:5444315 Doi  10.1016/j.cell.2012.08.036
Citation  Wang X, et al. (2012) TPC Proteins Are Phosphoinositide- Activated Sodium-Selective Ion Channels in Endosomes and Lysosomes. Cell 151(2):372-83
abstractText  Mammalian two-pore channel proteins (TPC1, TPC2; TPCN1, TPCN2) encode ion channels in intracellular endosomes and lysosomes and were proposed to mediate endolysosomal calcium release triggered by the second messenger, nicotinic acid adenine dinucleotide phosphate (NAADP). By directly recording TPCs in endolysosomes from wild-type and TPC double-knockout mice, here we show that, in contrast to previous conclusions, TPCs are in fact sodium-selective channels activated by PI(3,5)P(2) and are not activated by NAADP. Moreover, the primary endolysosomal ion is Na(+), not K(+), as had been previously assumed. These findings suggest that the organellar membrane potential may undergo large regulatory changes and may explain the specificity of PI(3,5)P(2) in regulating the fusogenic potential of intracellular organelles.
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