The Molecular Basis for Ca2+ Signalling by NAADP: Two-Pore Channels in a Complex?

Jonathan S Marchant; Yaping Lin-Moshier; Timothy F Walseth; Sandip Patel

doi:10.1166/msr.2012.1003

The Molecular Basis for Ca²⁺ Signalling by NAADP: Two-Pore Channels in a Complex?

Messenger (Los Angel). 2012 Jun 1;1(1):63-76. doi: 10.1166/msr.2012.1003.

Authors

Jonathan S Marchant¹, Yaping Lin-Moshier¹, Timothy F Walseth¹, Sandip Patel²

Affiliations

¹ Department of Pharmacology, University of Minnesota Medical School, MN 55455, USA.
² Department of Cell and Developmental Biology, University College London, WC1E 6BT, UK.

Abstract

NAADP is a potent Ca²⁺ mobilizing messenger in a variety of cells but its molecular mechanism of action is incompletely understood. Accumulating evidence indicates that the poorly characterized two-pore channels (TPCs) in animals are NAADP sensitive Ca²⁺-permeable channels. TPCs localize to the endo-lysosomal system but are functionally coupled to the better characterized endoplasmic reticulum Ca²⁺ channels to generate physiologically relevant complex Ca²⁺ signals. Whether TPCs directly bind NAADP is not clear. Here we discuss the idea based on recent studies that TPCs are the pore-forming subunits of a protein complex that includes tightly associated, low molecular weight NAADP-binding proteins.

Keywords: Ca2+ Signaling; Endosomes; Lysosomes; NAADP; Photoaffinity Labelling; Two-Pore Channels.

Abstract

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