Nicotinic Acid Adenine Dinucleotide Phosphate Potentiates Neurite Outgrowth

Abstract

Ca2؉ regulates a spectrum of cellular processes including many aspects of neuronal function. Ca 2؉ -sensitive events such as neurite extension and axonal guidance are driven by Ca 2؉ signals that are precisely organized in both time and space. These complex cues result from both Ca 2؉ influx across the plasma membrane and the mobilization of intracellular Ca 2؉ stores. In the present study, using rat cortical neurons, we have examined the effects of the novel intracellular Ca 2؉ -mobilizing messenger nicotinic acid adenine dinucleotide phosphate (NAADP) on neurite length and cytosolic Ca 2؉ levels. We show that NAADP potentiates neurite extension in response to serum and nerve growth factor and stimulates increases in cytosolic Ca 2؉ from bafilomycin-sensitive Ca 2؉ stores. Simultaneous blockade of inositol trisphosphate and ryanodine receptors abolished the effects of NAADP on neurite length and reduced the magnitude of NAADP-mediated Ca 2؉ signals. This is the first report demonstrating functional NAADP receptors in a mammalian neuron. Interplay between NAADP receptors and more established intracellular Ca 2؉ channels may therefore play important signaling roles in the nervous system.

Reconstitution and Characterization of a Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP)-sensitive Ca2+ Release Channel from Liver Lysosomes of Rats

“…This is not consistent with the observations in intact cells such as pancreatic acinar cells (45), pulmonary arterial myocytes (46), neurite (47), and coronary arterial myocytes (11), where bafilomycin A1 selectively inhibited NAADP-induced Ca 2ϩ release in the lysosomes. The reason for this difference may be associated with the mechanisms mediating lysosome Ca 2ϩ stores, which may be revealed differently in intact cells or isolated lysosomes of these cells.…”

Nicotinic acid adenine dinucleotide phosphate regulates skeletal muscle differentiation via action at two-pore channels

“…Therefore, it is clear that mechanisms that control the cytoplasmic calcium concentration are essential for induction of the myogenic differentiation program. NAADP has recently been evolving as a new universal second messenger, with a role in a variety of signaling cascades from fertilization (26)(27)(28), insulin secretion (26,29,30), T-cell activation (5,17), neurotransmitter secretion (31) and, most pertinently, neurite outgrowth (16,32) RNA was harvested at the indicated time points and analyzed using Northern blot for expression of RyR and TPC subtypes, using specific probes. Differentiation was monitored by detection of myogenin.…”

Ca2+Influx through Mechanosensitive Channels Inhibits Neurite Outgrowth in Opposition to Other Influx Pathways and Release from Intracellular Stores

“…Surprisingly, BAPTA alone does not stimulate neurite extension as occurs with elimination of extracellular Ca 2ϩ . This could be attributable to the effective buffering of all influx signals, those inhibiting and supporting growth, as well as buffering at sites of Ca 2ϩ release from intracellular stores, which have been shown to support neurite extension (Takei et al, 1998;Brailoiu et al, 2005;Ooashi et al, 2005) (Fig. 6).…”