The endo-lysosomal system as an NAADP-sensitive acidic Ca2+ store: Role for the two-pore channels

Sandip Patel, Latha Ramakrishnan, Taufiq Rahman, Amro Hamdoun, Jonathan S. Marchant, Colin W. Taylor, Eugen Brailoiu

Research output: Contribution to journalReview articlepeer-review

52 Scopus citations

Abstract

Accumulating evidence suggests that the endo-lysosomal system provides a substantial store of Ca2+ that is tapped by the Ca2+-mobilizing messenger, NAADP. In this article, we review evidence that NAADP-mediated Ca2+ release from this acidic Ca2+ store proceeds through activation of the newly described two-pore channels (TPCs). We discuss recent advances in defining the sub-cellular targeting, topology and biophysics of TPCs. We also discuss physiological roles and the evolution of this ubiquitous ion channel family.

Original languageEnglish (US)
Pages (from-to)157-167
Number of pages11
JournalCell Calcium
Volume50
Issue number2
DOIs
StatePublished - Aug 2011

Bibliographical note

Funding Information:
We thank Dev Churamani, Robert Hooper, Chi Li and Desmond Tobin for useful discussion, and the Bogue foundation (University College London) for facilitating staff exchange. Work in SP's laboratory is funded by the BBSRC . Work in CWT's laboratory is funded by the Wellcome Trust. TR is a Drapers’ Research Fellow at Pembroke College, Cambridge.

Keywords

  • Acidic calcium stores
  • Calcium
  • Endosomes
  • Lysosomes
  • NAADP
  • TPC1
  • TPC2
  • TPCN1
  • TPCN2
  • Two-pore channels

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