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NAADP-evoked Ca2+ signals through two-pore channel-1 require arginine residues in the first S4-S5 linker

Patel, S; Churamani, D; Brailoiu, E; (2017) NAADP-evoked Ca2+ signals through two-pore channel-1 require arginine residues in the first S4-S5 linker. Cell Calcium , 68 pp. 1-4. 10.1016/j.ceca.2017.09.003. Green open access

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Abstract

Two-pore channels (TPCs) are two-domain members of the voltage-gated ion channel superfamily that localize to acidic organelles. Their mechanism of activation (ligands such as NAADP/PI(3,5)P2 versus voltage) and ion selectivity (Ca(2+) versus Na(+)) is debated. Here we report that a cluster of arginine residues in the first domain required for selective voltage-gating of TPC1 map not to the voltage-sensing fourth transmembrane region (S4) but to a cytosolic downstream region (S4-S5 linker). These residues are conserved between TPC isoforms suggesting a generic role in TPC activation. Accordingly, mutation of residues in TPC1 but not the analogous region in the second domain prevents Ca(2+) release by NAADP in intact cells. Our data affirm the role of TPCs in NAADP-mediated Ca(2+) signalling and unite differing models of channel activation through identification of common domain-specific residues.

Type: Article
Title: NAADP-evoked Ca2+ signals through two-pore channel-1 require arginine residues in the first S4-S5 linker
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ceca.2017.09.003
Publisher version: http://dx.doi.org/10.1016/j.ceca.2017.09.003
Language: English
Additional information: © 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10038905
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