Recruitment of NAADP-sensitive acidic Ca2+ stores by glutamate

Abstract

NAADP (nicotinic acid–adenine dinucleotide phosphate) is an unusual second messenger thought to mobilize acidic Ca2+ stores, such as lysosomes or lysosome-like organelles, that are functionally coupled to the ER (endoplasmic reticulum). Although NAADP-sensitive Ca2+ stores have been described in neurons, the physiological cues that recruit them are not known. Here we show that in both hippocampal neurons and glia, extracellular application of glutamate, in the absence of external Ca2+, evoked cytosolic Ca2+ signals that were inhibited by preventing organelle acidification or following osmotic bursting of lysosomes. The sensitivity of both cell types to glutamate correlated well with lysosomal Ca2+ content. However, interfering with acidic compartments was largely without effect on the Ca2+ content of the ER or Ca2+ signals in response to ATP. Glutamate but not ATP elevated cellular NAADP levels. Our results provide evidence for the agonist-specific recruitment of NAADP-sensitive Ca2+ stores by glutamate. This links the actions of NAADP to a major neurotransmitter in the brain.

A Functional Role for Nicotinic Acid Adenine Dinucleotide Phosphate in Oxytocin-Mediated Contraction of Uterine Smooth Muscle from Rat

“…Our findings are consistent with a previous report showing a role for NAADP in oxytocin-induced calcium increases in isolated human myometrial cells (Soares et al, 2007). Combining our results reported here with previously published studies Yamasaki et al, 2005;Soares et al, 2007;Pandey et al, 2009) highlights the need to consider potential action of NAADP, even in G protein-signaling pathways that are traditionally linked to InsP 3 signaling.…”

“…These data provided clear evidence that complete oxytocin-induced contractions require both NAADP and InsP 3 . We hypothesize that the action of oxytocin at its receptor results in production of both InsP 3 and NAADP, as reported for several other G protein-coupled receptors (Cancela et al, 1999;Yamasaki et al, 2005;Soares et al, 2007;Pandey et al, 2009). NAADP produces a local release of calcium from acidic organelles, which is then amplified by InsP 3 and its receptors to provide a global release (Cancela et al, 1999).…”

“…This research has established NAADP as a unique calcium-signaling molecule (Patel, 2004;Lee, 2005;Galione et al, 2009) that releases calcium from a store independent of InsP 3 and cADPR (Genazzani and Galione, 1996;Lee, 2000). Indeed, a number of recent studies have demonstrated that G protein-coupled signaling can occur not only via InsP 3 but also through a NAADP component Yamasaki et al, 2005;Macgregor et al, 2007;Naylor et al, 2009), which surprisingly includes the classical neurotransmitter glutamate (Pandey et al, 2009).…”

Acidic NAADP-sensitive Calcium Stores in the Endothelium

“…2D (36), and ATP was shown to act largely independently of acidic stores in hippocampal neurons and glia (37). This is the first report implicating acidic Ca 2ϩ stores in acetylcholine action.…”

The Ecto-enzyme CD38 Is a Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) Synthase That Couples Receptor Activation to Ca2+ Mobilization from Lysosomes in Pancreatic Acinar Cells

“…Dramatic increases in NAADP occur during sea urchin egg fertilization due to production in sperm upon contacting egg jelly (14). Increases in NAADP levels have been also reported in pancreatic ␤-cells after glucose (15) and glucagon-like peptide-1 stimulation (17), in pancreatic acinar cells after CCK stimulation (16), in pulmonary smooth muscle following exposure to endothelin-1 (3), in response to histamine in human myometrial cells (18), and glutamate in neurones (19). However, the enzymes responsible for endogenous NAADP synthesis in vivo remain to be clearly identified (20), although members of the ADP-ribosyl cyclase family are possibly involved because the purified CD38 and Aplysia ADP-ribosyl cyclases have been shown to be capable of NAADP synthesis in vitro (21)(22)(23).…”