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Expression of Ca²⁺-permeable two-pore channels rescues NAADP signalling in TPC-deficient cells.

Abstract:

The second messenger NAADP triggers Ca2+ release from endo‐lysosomes. Although two‐pore channels (TPCs) have been proposed to be regulated by NAADP, recent studies have challenged this. By generating the first mouse line with demonstrable absence of both Tpcn1 and Tpcn2 expression (Tpcn1/2−/−), we show that the loss of endogenous TPCs abolished NAADP‐dependent Ca2+ responses as assessed by single‐cell Ca2+ imaging or patch‐clamp of single endo‐lysosomes. In contrast, currents stimulated by PI...

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Publication status:
Published
Peer review status:
Peer reviewed
Version:
Accepted manuscript

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Publisher copy:
10.15252/embj.201490009

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Institution:
University of Oxford
Department:
Oxford, MSD, Pharmacology
More by this author
Institution:
University of Oxford
Department:
Oxford, MSD, Pharmacology
More by this author
Institution:
University of Oxford
Department:
Oxford, MSD, Pharmacology
More by this author
Institution:
University of Oxford
Department:
Oxford, MSD, Pharmacology
More by this author
Institution:
University of Oxford
Department:
Oxford, MSD, Pharmacology
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Publisher:
EMBO Press Publisher's website
Journal:
The EMBO Journal Journal website
DOI:
ISSN:
1460-2075
URN:
uuid:bbf91b76-a4dd-4e54-9520-48289683b72a
Source identifiers:
608739
Local pid:
pubs:608739

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