Medical College of Wisconsin
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Two-pore channels: Regulation by NAADP and customized roles in triggering calcium signals. Cell Calcium 2010 Jun;47(6):480-90

Date

07/14/2010

Pubmed ID

20621760

Pubmed Central ID

PMC2921607

DOI

10.1016/j.ceca.2010.05.001

Scopus ID

2-s2.0-77953916412 (requires institutional sign-in at Scopus site)   81 Citations

Abstract

NAADP is a potent regulator of cytosolic calcium levels. Much evidence suggests that NAADP activates a novel channel located on an acidic (lysosomal-like) calcium store, the mobilisation of which results in further calcium release from the endoplasmic reticulum. Here, we discuss the recent identification of a family of poorly characterized ion channels (the two-pore channels) as endo-lysosomal NAADP receptors. The generation of calcium signals by these channels is likened to those evoked by depolarisation during excitation-contraction coupling in muscle. We discuss the idea that two-pore channels can mediate a trigger release of calcium which is then amplified by calcium-induced calcium release from the endoplasmic reticulum. This is similar to the activation of voltage-sensitive calcium channels and subsequent mobilisation of sarcoplasmic reticulum calcium stores in cardiac tissue. We suggest that two-pore channels may physically interact with ryanodine receptors to account for more direct release of calcium from the endoplasmic reticulum in analogy with the conformational coupling of voltage-sensitive calcium channels and ryanodine receptors in skeletal muscle. Interaction of two-pore channels with other calcium release channels likely occurs between stores "trans-chatter" and possibly within the same store "cis-chatter". We also speculate that trafficking of two-pore channels through the endo-lysosomal system facilitates interactions with calcium entry channels. Strategic placing of two-pore channels thus provides a versatile means of generating spatiotemporally complex cellular calcium signals.

Author List

Patel S, Marchant JS, Brailoiu E

Author

Jonathan S. Marchant PhD Chair, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Calcium
Calcium Signaling
Endoplasmic Reticulum
Humans
Ion Channels
NADP
Ryanodine Receptor Calcium Release Channel