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, 40 (1), 153-7

Triggering of Ca2+ Signals by NAADP-gated Two-Pore Channels: A Role for Membrane Contact Sites?

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Triggering of Ca2+ Signals by NAADP-gated Two-Pore Channels: A Role for Membrane Contact Sites?

Sandip Patel et al. Biochem Soc Trans.

Abstract

NAADP (nicotinic acid-adenine dinucleotide phosphate) is a potent Ca2+-mobilizing messenger implicated in many Ca2+-dependent cellular processes. It is highly unusual in that it appears to trigger Ca2+ release from acidic organelles such as lysosomes. These signals are often amplified by archetypal Ca2+ channels located in the endoplasmic reticulum. Recent studies have converged on the TPCs (two-pore channels) which localize to the endolysosomal system as the likely primary targets through which NAADP mediates its effects. 'Chatter' between TPCs and endoplasmic reticulum Ca2+ channels is disrupted when TPCs are directed away from the endolysosomal system. This suggests that intracellular Ca2+ release channels may be closely apposed, possibly at specific membrane contact sites between acidic organelles and the endoplasmic reticulum.

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