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

ABSTRACT: 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.

SUBMITTER: Wang X

PROVIDER: S-EPMC3475186 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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

Wang Xiang X Zhang Xiaoli X Dong Xian-Ping XP Samie Mohammad M Li Xinran X Cheng Xiping X Goschka Andrew A Shen Dongbiao D Zhou Yandong Y Harlow Janice J Zhu Michael X MX Clapham David E DE Ren Dejian D Xu Haoxing H

Cell 20121001 2

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 ac ...[more]

PMID: 23063126

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