Both p140  and p75NGFR Nerve Growth Factor Receptors Mediate Nerve Growth Factor-stimulated Calcium Uptake

Jiang, Hao; Ulme, Danielle St.; Dickens, Geneva; Chabuk, Alia; Lavarreda, Miriam; Lazarovici, Philip; Guroff, Gordon

doi:10.1074/jbc.272.11.6835

Cited by 29 publications

(21 citation statements)

References 41 publications

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“…However, some reports have indicated that NGF and EGF are able to induce a small and rapid increase in [Ca 2ϩ ] i (57,65,80,92; reviewed in reference 47). More recent results have reported that NGF-induced increases in [Ca 2ϩ ] i seem to arise from both intracellular stores and extracellular spaces being mediated by the Trk receptor (16,48,75). However, in those reports, the functional relevance of Ca 2ϩ mobilization after NGF stimulation was not clear.…”

Section: Discussionmentioning

confidence: 75%

Nerve Growth Factor Activation of the Extracellular Signal-Regulated Kinase Pathway Is Modulated by Ca²⁺and Calmodulin

Egea

Espinet

Soler

et al. 2000

Molecular and Cellular Biology

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Nerve growth factor is a member of the neurotrophin family of trophic factors that have been reported to be essential for the survival and development of sympathetic neurons and a subset of sensory neurons. Nerve growth factor exerts its effects mainly by interaction with the specific receptor TrkA, which leads to the activation of several intracellular signaling pathways. Once activated, TrkA also allows for a rapid and moderate increase in intracellular calcium levels, which would contribute to the effects triggered by nerve growth factor in neurons. In this report, we analyzed the relationship of calcium to the activation of the Ras/extracellular signal-regulated kinase pathway in PC12 cells. We observed that calcium and calmodulin are both necessary for the acute activation of extracellular signal-regulated kinases after TrkA stimulation. We analyzed the elements of the pathway that lead to this activation, and we observed that calmodulin antagonists completely block the initial Raf-1 activation without affecting the function of upstream elements, such as Ras, Grb2, Shc, and Trk. We have broadened our study to other stimuli that activate extracellular signal-regulated kinases through tyrosine kinase receptors, and we have observed that calmodulin also modulates the activation of such kinases after epidermal growth factor receptor stimulation in PC12 cells and after TrkB stimulation in cultured chicken embryo motoneurons. Calmodulin seems to regulate the full activation of Raf-1 after Ras activation, since functional Ras is necessary for Raf-1 activation after nerve growth factor stimulation and calmodulin-Sepharose is able to precipitate Raf-1 in a calcium-dependent manner.Neurotrophins (NTs) are neurotrophic factors involved in the development, maintenance, and repair of the nervous system (reviewed in reference 60). This family is composed of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 and neurotrophin 4/5. NGF was the first NT described and has been shown to be essential for the survival and development of sympathetic neurons, some sensory neurons, and a population of cholinergic cells located at the basal forebrain (14,39,94). Each of these NTs exhibits trophic effects on a specific, although partially overlapping, subset of neuronal populations in either the central or the peripheral nervous system both in vivo and in vitro (6, 15). NTs bind to two types of receptors, p75LNTR and the Trk family of tyrosine kinases. All NTs bind to p75 LNTR . However, they show a high degree of specificity for Trk receptors. TrkA is the preferential receptor for NGF, TrkB is that for BDNF and neurotrophin 4/5, and TrkC is that for neurotrophin 3 (5). In the last few years, much attention has been focused on ascertaining the molecular mechanism by which Trk signaling mediates the effects of NTs.The paradigm for studying the intracellular signaling pathways underlying TrkA activation has been the stimulation of this receptor with NGF in the PC12 cell line (38). Once phosphorylated, T...

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Section: Discussionmentioning

confidence: 75%

Nerve Growth Factor Activation of the Extracellular Signal-Regulated Kinase Pathway Is Modulated by Ca²⁺and Calmodulin

Egea

Espinet

Soler

et al. 2000

Molecular and Cellular Biology

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“…The pCMV-trkA expression plasmid (36) and the pCMV5-p75 expression plasmid (kindly provided by Dr. Moses Chao) were transfected separately into NIH 3T3 cells by the calcium phosphate method as described previously (36). The stable clones WT11, L2, and L9 were selected in 0.5 mg/ml G418 and were used in the present studies.…”

Section: Methodsmentioning

confidence: 99%

“…In a previous study it was shown that NGF induced an increased uptake of calcium into 3T3 cells stably transfected with either p140 trk or p75 NGFR (36). In the present study we used confocal microscopy to investigate further the alterations in calcium levels produced by NGF in these two separate cell populations.…”

mentioning

confidence: 99%

Nerve Growth Factor (NGF)-induced Calcium Influx and Intracellular Calcium Mobilization in 3T3 Cells Expressing NGF Receptors

Jiang

Takeda

Lazarovici

et al. 1999

Journal of Biological Chemistry

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The neurotrophins have been implicated in the acute regulation of synaptic plasticity. Neurotrophin-stimulated presynaptic calcium uptake appears to play a key role in this process. To understand the mechanism of neurotrophin-stimulated calcium uptake, the regulation of calcium uptake and intracellular mobilization by nerve growth factor (NGF) was investigated using NIH 3T3 cells stably transfected with either the high affinity NGF receptor p140 trk (3T3-Trk) or the low affinity NGF receptor p75 NGFR (3T3-p75). In 3T3-Trk cells, NGF increased both calcium uptake and intracellular calcium mobilization. In 3T3-p75 cells, NGF increased calcium uptake but not intracellular calcium mobilization. K-252a alone increased intracellular calcium in 3T3-Trk cells but not in 3T3-p75 cells. Nifedipine, an inhibitor of calcium uptake through L-type calcium channels, inhibited the action of NGF on both 3T3-Trk cells and 3T3-p75 cells, indicating that both p140trk and p75 NGFR receptors are linked to nifedipine-sensitive L-type calcium channels. These studies show that either NGF receptor will support increases in intracellular calcium but that p140 trk does so by increasing both uptake and mobilization, whereas p75 NGFR does so by increasing uptake only.

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“…NGF can mediate increases in cytoplasmic C a 2ϩ concentration (De Bernardi et al, 1996;Jian et al, 1997). Therefore, we investigated the involvement of cytoplasmic [C a 2ϩ ] in the induction of filopodial sprouts by NGF-coated beads.…”

Section: Role Of Ca 2ϩ Fluxesmentioning

confidence: 99%

Localized Sources of Neurotrophins Initiate Axon Collateral Sprouting

1998

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The sprouting of axon collateral branches is important in the establishment and refinement of neuronal connections during both development and regeneration. Collateral branches are initiated by the appearance of localized filopodial activity along quiescent axonal shafts. We report here that sensory neuron axonal shafts rapidly sprout filopodia at sites of contact with nerve growth factor-coated polystyrene beads. Some sprouts can extend up to at least 60 m through multiple bead contacts. Axonal filopodial sprouts often contained microtubules and exhibited a debundling of axonal microtubules at the site of bead-axon contact. Cytochalasin treatment abolished the filopodial sprouting, but not the accumulation of actin filaments at sites of bead-axon contact. The axonal sprouting response is mediated by the trkA receptor and likely acts through a phosphoinositide-3 kinase-dependent pathway, in a manner independent of intracellular Ca 2ϩ fluctuations. These findings implicate neurotrophins as local cues that directly stimulate the formation of collateral axon branches.

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Both p140 and p75NGFR Nerve Growth Factor Receptors Mediate Nerve Growth Factor-stimulated Calcium Uptake

Cited by 29 publications

References 41 publications

Nerve Growth Factor Activation of the Extracellular Signal-Regulated Kinase Pathway Is Modulated by Ca²⁺and Calmodulin

Nerve Growth Factor Activation of the Extracellular Signal-Regulated Kinase Pathway Is Modulated by Ca²⁺and Calmodulin

Nerve Growth Factor (NGF)-induced Calcium Influx and Intracellular Calcium Mobilization in 3T3 Cells Expressing NGF Receptors

Localized Sources of Neurotrophins Initiate Axon Collateral Sprouting

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Both p140 and p75NGFR Nerve Growth Factor Receptors Mediate Nerve Growth Factor-stimulated Calcium Uptake

Cited by 29 publications

References 41 publications

Nerve Growth Factor Activation of the Extracellular Signal-Regulated Kinase Pathway Is Modulated by Ca2+and Calmodulin

Nerve Growth Factor Activation of the Extracellular Signal-Regulated Kinase Pathway Is Modulated by Ca2+and Calmodulin

Nerve Growth Factor (NGF)-induced Calcium Influx and Intracellular Calcium Mobilization in 3T3 Cells Expressing NGF Receptors

Localized Sources of Neurotrophins Initiate Axon Collateral Sprouting

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Nerve Growth Factor Activation of the Extracellular Signal-Regulated Kinase Pathway Is Modulated by Ca²⁺and Calmodulin

Nerve Growth Factor Activation of the Extracellular Signal-Regulated Kinase Pathway Is Modulated by Ca²⁺and Calmodulin