Calcium regulation of gene expression in neurons: the mode of entry matters

Gallin, Warren J.; Greenberg, Michael E.

doi:10.1016/0959-4388(95)80050-6

Cited by 117 publications

(71 citation statements)

References 57 publications

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Section: Methodsmentioning

confidence: 99%

“…The establishment of the PC12 cell clone 15-1/5, which stably expresses tTA, will be described elsewhere. 2 To generate a PC12/HER-CD533 construct, the HER-CD533 cDNA was subcloned as an EcoRI fragment into pUHD10-3.Cell Culture and Generation of PC12 Cell Lines-PC12 cells (kindly provided by Philip Cohen) were cultured in Dulbecco's modified Eagle's medium, 4500 g/liter glucose, supplemented with 5% fetal bovine serum and 10% horse serum. PC12 cells were generally grown on collagen (Sigma)-coated plasic dishes.…”

mentioning

confidence: 99%

“…Intracellular calcium levels are modulated either by release of calcium from internal stores or by calcium entry across the plasma membrane through ligand-or voltage-gated calcium channels (1)(2)(3). Stimuli such as membrane depolarization result in activation of L-type voltage-sensitive calcium channels, leading to calcium-mediated induction of a specific set of genes and thereby contributing to physiological responses such as neuronal differentiation and survival (4) .…”

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confidence: 99%

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Critical Role of Calcium- dependent Epidermal Growth Factor Receptor Transactivation in PC12 Cell Membrane Depolarization and Bradykinin Signaling

Zwick

Daub

Aoki

et al. 1997

Journal of Biological Chemistry

190

143

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PC12 cells respond to a variety of external stimuli such as growth factors, neurotransmitters, and membrane depolarization by activating the Ras/mitogen-activated protein kinase pathway. Here we demonstrate that both depolarization-induced calcium influx and treatment with bradykinin stimulate tyrosine phosphorylation of the epidermal growth factor receptor (EGFR). Using a tetracycline-controlled expression system in conjunction with a dominant-negative EGFR mutant, we demonstrate that depolarization and bradykinin triggered signals involve EGFR function upstream of SHC and MAP kinase. Furthermore, bradykinin-stimulated EGFR transactivation is critically dependent on the presence of extracellular calcium, and when triggered by ionophore treatment, calcium influx is already sufficient to induce EGFR tyrosine phosphorylation. Taken together, our results establish calcium-dependent EGFR transactivation as a signaling mechanism mediating activation of the Ras/mitogen-activated protein kinase pathway in neuronal cell types.In neurons, the cytosolic calcium concentration is tightly regulated and represents a critical parameter for a variety of intracellular signaling processes. Intracellular calcium levels are modulated either by release of calcium from internal stores or by calcium entry across the plasma membrane through ligand-or voltage-gated calcium channels (1-3). Stimuli such as membrane depolarization result in activation of L-type voltage-sensitive calcium channels, leading to calcium-mediated induction of a specific set of genes and thereby contributing to physiological responses such as neuronal differentiation and survival (4) .Before altering gene expression, elevation of intracellular calcium levels can trigger various signaling events, among them the activation of the small G-protein Ras resulting in stimulation of the mitogen-activated protein kinase (MAPK) 1 pathway (5). In PC12 cells, a rat pheochromocytoma cell line widely used as a model system for neuronal differentiation, calcium influx rapidly induces tyrosine phosphorylation of the adaptor protein SHC and SHC-Grb2 complex formation, steps known to couple cell surface receptors such as receptor tyrosine kinases to Ras (6). Using a PC12 subline overexpressing a dominant-negative mutant of the cytoplasmatic tyrosine kinase Src, Rusanescu et al. found that inhibiton of membrane depolarization induced SHC tyrosine phosphorylation and MAPK activation (7). Moreover calcium influx following membrane depolarization was recently reported to mediate ligandindependent epidermal growth factor receptor (EGFR) tyrosine phosphorylation in this system (8). Although direct evidence is lacking regarding whether this represents an essential signaling event for activation of the MAPK pathway, this finding raises the possibility that in PC12 cells calcium may play a role in the EGFR transactivation mechanism as previously demonstrated for signaling through G-protein coupled receptor (GPCR) in Rat-1 fibroblasts (9). In addition to membrane depolarization-induced acti...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Critical Role of Calcium- dependent Epidermal Growth Factor Receptor Transactivation in PC12 Cell Membrane Depolarization and Bradykinin Signaling

Zwick

Daub

Aoki

et al. 1997

Journal of Biological Chemistry

190

143

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“…Furthermore, VGCCs represent a major Ca 2ϩ entry pathway even during the physiological activation of ligand-gated Ca 2ϩ channels (Miyakawa et al, 1992;Jaffe et al, 1994;Regehr and Tank, 1994;Stuart and Sakmann, 1994;Magee and Johnston, 1995;Yuste and Denk, 1995). It also is becoming clear that Ca 2ϩ influx via different routes (voltage vs ligand-gated channel influx) may not be functionally interchangeable (Gallin and Greenberg, 1995;. Therefore, it seems important to determine the nature of any changes that may occur in VGCCs over time in hippocampal neurons and to test the possibility that some aspects of these changes are related to increasing vulnerability and greater probability of death.…”

Section: Abstract: Hippocampal Neurons; Calcium Currents; Cell Deathmentioning

confidence: 99%

Calcium Channel Density and Hippocampal Cell Death with Age in Long-Term Culture

et al. 1997

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The expression of voltage-gated calcium (Ca 2ϩ ) channel activity in brain cells is known to be important for several aspects of neuronal development. In addition, excessive Ca 2ϩ influx has been linked clearly to neurotoxicity both in vivo and in vitro; however, the temporal relationship between the development of Ca 2ϩ channel activity and neuronal survival is not understood. Over a period spanning 28 d in vitro, progressive increases in high voltage-activated whole-cell Ca 2ϩ current and L-type Ca 2ϩ channel activity were observed in cultured hippocampal neurons. On the basis of single-channel analyses, these increases seem to arise in part from a greater density of functionally available L-type Ca 2ϩ channels. An increase in mRNA for the ␣ 1 subunit of L-type Ca 2ϩ channels occurred over a similar time course, which suggests that a change in gene expression may underlie the increased channel density. Parallel studies showed that hippocampal neuronal survival over 28 d was inversely related to increasing Ca 2ϩ current density. Chronic treatment of hippocampal neurons with the L-type Ca 2ϩ channel antagonist nimodipine significantly enhanced survival. Together, these results suggest that age-dependent increases in the density of Ca 2ϩ channels might contribute significantly to declining viability of hippocampal neurons. The results also are analogous to patterns seen in neurons of aged animals and therefore raise the possibility that long-term primary neuronal culture could serve as a model for some aspects of aging changes in hippocampal Ca 2ϩ channel function.

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“…Depending on subunit composition, nicotinic acetylcholine receptors have calcium permeability greater than that of NMDA receptors (Pugh and Berg, 1994;Rathouz and Berg, 1994;Role and Berg, 1996). Given the many regulatory roles of intracellular calcium elevation, in shortand long-term synaptic plasticity (Ghosh and Greenberg, 1995), regulation of neuronal process outgrowth, and regulation of ion channels, receptors, and enzyme activities as well as transcriptional cascades (Gallin and Greenberg, 1995), nicotinic and serotonergic receptor activation are poised to participate in the regulation of cortical plasticity through diverse pathways. In addition, nACh receptors presynaptically regulate the release of the conventional fast transmitters glutamate and GABA (Role and Berg, 1996), which further implicates them in regulating synaptic function in developing and mature cortex.…”

Section: Possible Functions Of Ionotropic Acetylcholine and Serotoninmentioning

confidence: 99%

Fast Synaptic Signaling by Nicotinic Acetylcholine and Serotonin 5-HT₃Receptors in Developing Visual Cortex

1997

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Cholinergic and serotonergic fiber systems invade the developing visual cortex several weeks before eye opening; both transmitters have been implicated in plasticity of neocortical circuits. These transmitters have been presumed to act predominantly through second messenger-coupled receptors, because fast cholinergic or serotonergic neurotransmission has never been observed in neocortex. However, acetylcholine and serotonin also act on ligand-gated ion channels; the nicotinic acetylcholine receptor and the serotonin 5-HT 3 receptor, respectively. Here, using whole-cell patch-clamp techniques in developing ferret visual cortex, we pharmacologically isolated fast, spontaneous, and evoked cholinergic and serotonergic synaptic events in pyramidal cells and interneurons of all cortical layers. The number of cells receiving such inputs increased with the ingrowth of thalamic afferents, and the frequencies of the spontaneous events increased at eye opening. Thus, both acetylcholine and serotonin can mediate fast synaptic transmission in the visual cortex; the early onset of these mechanisms suggests a role during initial stages of circuit formation and during subsequent experience-dependent remodeling of cortical connections.

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Calcium regulation of gene expression in neurons: the mode of entry matters

Cited by 117 publications

References 57 publications

Critical Role of Calcium- dependent Epidermal Growth Factor Receptor Transactivation in PC12 Cell Membrane Depolarization and Bradykinin Signaling

Critical Role of Calcium- dependent Epidermal Growth Factor Receptor Transactivation in PC12 Cell Membrane Depolarization and Bradykinin Signaling

Calcium Channel Density and Hippocampal Cell Death with Age in Long-Term Culture

Fast Synaptic Signaling by Nicotinic Acetylcholine and Serotonin 5-HT₃Receptors in Developing Visual Cortex

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Calcium regulation of gene expression in neurons: the mode of entry matters

Cited by 117 publications

References 57 publications

Critical Role of Calcium- dependent Epidermal Growth Factor Receptor Transactivation in PC12 Cell Membrane Depolarization and Bradykinin Signaling

Critical Role of Calcium- dependent Epidermal Growth Factor Receptor Transactivation in PC12 Cell Membrane Depolarization and Bradykinin Signaling

Calcium Channel Density and Hippocampal Cell Death with Age in Long-Term Culture

Fast Synaptic Signaling by Nicotinic Acetylcholine and Serotonin 5-HT3Receptors in Developing Visual Cortex

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Product

Resources

About

Fast Synaptic Signaling by Nicotinic Acetylcholine and Serotonin 5-HT₃Receptors in Developing Visual Cortex