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TPC Proteins Are Phosphoinositide- Activated Sodium-Selective Ion Channels in Endosomes and Lysosomes
Open accessAbstract
Summary Mammalian Two-Pore Channels (TPC1, 2; 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)P2, 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)P2 in regulating the fusogenic potential of intracellular organelles.
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[6] Correction for liquid junction potentials in patch clamp experiments
Neher, E. (1992) · Methods in Enzymology · doi:10.1016/0076-6879(92)07008-c · Cited by 1,132
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Calcraft, P. J., Ruas, M., Pan, Z., Cheng, X., Arredouani, A., Hao, X., Tang, J., Rietdorf, K., Teboul, L., Chuang, K.-T., et al. (2009) · Nature · doi:10.1038/nature08030 · Cited by 760
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Metadata
- Authors
- Wang, X., Zhang, X., Dong, X.-P., Samie, M., Li, X., Cheng, X., Goschka, A., Shen, D., Zhou, Y., Harlow, J., Zhu, M. X., Clapham, D. E., Ren, D., & Xu, H.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 151
- Issue
- 2
- Pages
- 372-383
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2075094914
- Cited by
- 530
- References
- 5
- FWCI
- 28.15
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Wang, X., Zhang, X., Dong, X.-P., Samie, M., Li, X., Cheng, X., Goschka, A., Shen, D., Zhou, Y., Harlow, J., Zhu, M. X., Clapham, D. E., Ren, D., & Xu, H. (2012). TPC Proteins Are Phosphoinositide- Activated Sodium-Selective Ion Channels in Endosomes and Lysosomes. Cell. https://doi.org/10.1016/j.cell.2012.08.036
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