The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
The two-pore channel TPCN2 mediates NAADP-dependent Ca2+-release from lysosomal stores
Open accessAbstract
Second messenger-induced Ca(2+)-release from intracellular stores plays a key role in a multitude of physiological processes. In addition to 1,4,5-inositol trisphosphate (IP(3)), Ca(2+), and cyclic ADP ribose (cADPR) that trigger Ca(2+)-release from the endoplasmatic reticulum (ER), nicotinic acid adenine dinucleotide phosphate (NAADP) has been identified as a cellular metabolite that mediates Ca(2+)-release from lysosomal stores. While NAADP-induced Ca(2+)-release has been found in many tissues and cell types, the molecular identity of the channel(s) conferring this release remained elusive so far. Here, we show that TPCN2, a novel member of the two-pore cation channel family, displays the basic properties of native NAADP-dependent Ca(2+)-release channels. TPCN2 transcripts are widely expressed in the body and encode a lysosomal protein forming homomers. TPCN2 mediates intracellular Ca(2+)-release after activation with low-nanomolar concentrations of NAADP while it is desensitized by micromolar concentrations of this second messenger and is insensitive to the NAADP analog nicotinamide adenine dinucleotide phosphate (NADP). Furthermore, TPCN2-mediated Ca(2+)-release is almost completely abolished when the capacity of lysosomes for storing Ca(2+) is pharmacologically blocked. By contrast, TPCN2-specific Ca(2+)-release is unaffected by emptying ER-based Ca(2+) stores. In conclusion, these findings indicate that TPCN2 is a major component of the long-sought lysosomal NAADP-dependent Ca(2+)-release channel.
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La Rovere, R. M. L., Roest, G., Bultynck, G., & Parys, J. B. (2016) · Cell Calcium · doi:10.1016/j.ceca.2016.04.005 · Cited by 257
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Regulation of lysosomal ion homeostasis by channels and transporters
Xiong, J., & Zhu, M. X. (2016) · Science China Life Sciences · doi:10.1007/s11427-016-5090-x · Cited by 141
Tong, B. C.-K., Wu, A. J., Huang, A. S., Dong, R., Malampati, S., Iyaswamy, A., Krishnamoorthi, S., Sreenivasmurthy, S. G., Zhu, Z., Su, C., et al. (2022) · Autophagy · doi:10.1080/15548627.2021.1945220 · Cited by 49
Metadata
- Authors
- Zong, X., Schieder, M., Cuny, H., Fenske, S., Gruner, C., Rötzer, K., Griesbeck, O., Harz, H., Biel, M., & Wahl-Schott, C.
- Venue
- Pflügers Archiv - European Journal of Physiology
- Published
- 2009-06-26
- Volume
- 458
- Issue
- 5
- Pages
- 891-899
- ISSN
- 0031-6768 (ISSN-L)
- 1432-2013
- OpenAlex
- W1975832881
- Cited by
- 275
- References
- 34
- FWCI
- 12.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Zong, X., Schieder, M., Cuny, H., Fenske, S., Gruner, C., Rötzer, K., Griesbeck, O., Harz, H., Biel, M., & Wahl-Schott, C. (2009). The two-pore channel TPCN2 mediates NAADP-dependent Ca2+-release from lysosomal stores. Pflügers Archiv - European Journal of Physiology. https://doi.org/10.1007/s00424-009-0690-y
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