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          Institute: MPI für Neurobiologie     Collection: Systems and Computational Neurobiology     Display Documents

ID: 434544.0, MPI für Neurobiologie / Systems and Computational Neurobiology
The two-pore channel TPCN2 mediates NAADP-dependent Ca2+-release from lysosomal stores
Authors:Zong, X. G.; Schieder, M.; Cuny, H.; Fenske, S.; Gruner, C.; Rötzer, K.; Griesbeck, O.; Harz, H.; Biel, M.; Wahl-Schott, C.
Date of Publication (YYYY-MM-DD):2009-09
Title of Journal:Pflügers Archiv-European Journal of Physiology
Journal Abbrev.:Pflügers Arch.
Issue / Number:5
Start Page:891
End Page:899
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:Second messenger-induced Ca2+-release from intracellular stores plays a key role in a multitude of physiological processes. In addition to 1,4,5-inositol trisphosphate (IP3), Ca2+, and cyclic ADP ribose (cADPR) that trigger Ca2+-release from the endoplasmatic reticulum (ER), nicotinic acid adenine dinucleotide phosphate (NAADP) has been identified as a cellular metabolite that mediates Ca2+-release from lysosomal stores. While NAADP-induced Ca2+-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 Ca2+-release channels. TPCN2 transcripts are widely expressed in the body and encode a lysosomal protein forming homomers. TPCN2 mediates intracellular Ca2+-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 Ca2+-release is almost completely abolished when the capacity of lysosomes for storing Ca2+ is pharmacologically blocked. By contrast, TPCN2-specific Ca2+-release is unaffected by emptying ER-based Ca2+ stores. In conclusion, these findings indicate that TPCN2 is a major component of the long-sought lysosomal NAADP-dependent Ca2+-release channel.
Free Keywords:TPCN2; Two-pore channels; NAADP; Ca2+-release; Lysosome; Acidic stores
External Publication Status:published
Document Type:Article
Affiliations:MPI für Neurobiologie/Systems and Computational Neurobiology (Borst)/Cellular Dynamics (Griesbeck)
External Affiliations:[Zong, Xiangang; Schieder, Michael; Cuny, Hartmut; Fenske, Stefanie; Gruner, Christian; Roetzer, Katrin; Biel, Martin; Wahl-Schott, Christian] Univ Munich, Dept Pharm, Zentrum Pharmaforsch, D-81377 Munich, Germany.; [Harz, Hartmann] Univ Munich, BioImaging Zentrum, D-81377 Munich, Germany.; [Zong, Xiangang; Schieder, Michael; Cuny, Hartmut; Fenske, Stefanie; Gruner, Christian; Roetzer, Katrin; Biel, Martin; Wahl-Schott, Christian] Univ Munich, Ctr Integrated Prot Sci CIPS M, D-81377 Munich, Germany.
Identifiers:ISI:000268584600007 [ID No:1]
ISSN:0031-6768 [ID No:2]
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