Abstract
Ca(2+) 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.
Highlights
Changes in cytosolic Ca2ϩ concentration regulate a whole host of cellular processes [1]
In the present study, using rat cortical neurons, we have examined the effects of the novel intracellular Ca2؉mobilizing messenger nicotinic acid adenine dinucleotide phosphate (NAADP) on neurite length and cytosolic Ca2؉ levels
Recent evidence suggests that in addition to inositol trisphosphate [4, 5] and ryanodine [6] receptors, which mediate the release of Ca2ϩ from theendoplasmic reticulum, intracellular Ca2ϩ channels sensitive to nicotinic acid adenine dinucleotide phosphate (NAADP)1 may be involved in the control of Ca2ϩ dynamics [7,8,9]
Summary
The underlying signal transduction pathways, are not well defined, Ca2ϩ is likely to play key roles [17] Both spontaneous entry of Ca2ϩ across the plasma membrane and Ca2ϩ entry in response to guidance cues such as cell adhesion molecules are crucial for various aspects of neuronal growth [18]. In addition to the well-characterized role of Ca2ϩ influx, the mobilization of intracellular Ca2ϩ stores through activation of both inositol trisphosphate [20, 21] and ryanodine [22, 23] receptors has been implicated in the control of neuronal growth.
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