Extracellular-signal-regulated kinase signalling in neurons

Grewal, Savraj; York, Randall D.; Stork, Philip J.S.

doi:10.1016/s0959-4388(99)00010-0

Cited by 520 publications

(418 citation statements)

References 109 publications

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“…In this system, ERK is persistently activated after the formation of a stable upstream complex between the small G-protein Rap-1 and B-raf, an MEK activator (York et al, 1998). Alternatively, ERK may be retained in a constitutively activated state after its dimerization and nuclear translocation (Impey et al, 1998;Grewal et al, 1999). ERK is rapidly activated in response to HFS-LTP in the CA1 region Sweatt, 1996, 1997;Impey et al, 1998) and dentate gyrus (Coogan et al, 1999;Maguire et al, 1999;Davis et al, 2000;Rosenblum et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…ERK has many potential cytosolic substrates, however, and several rapid ERK-dependent mechanisms could be involved (Grewal et al, 1999). One intriguing scenario is that ERK and p38 stimulate protein synthesis at the post-transcriptional level through activation of the Ser/Thr kinase Mnk1 and subsequent phosphorylation of eukaryotic initiation factor 4E (Sonenberg and Gingras, 1998).…”

Section: Discussionmentioning

confidence: 99%

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Brain-Derived Neurotrophic Factor Induces Long-Term Potentiation in Intact Adult Hippocampus: Requirement for ERK Activation Coupled to CREB and Upregulation ofArcSynthesis

Ying

Futter²,

Rosenblum³

et al. 2002

J. Neurosci.

673

520

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Brain-derived neurotrophic factor (BDNF) is implicated in longterm synaptic plasticity in the adult hippocampus, but the cellular mechanisms are little understood. Here we used intrahippocampal microinfusion of BDNF to trigger long-term potentiation (BDNF-LTP) at medial perforant path-granule cell synapses in vivo. BDNF infusion led to rapid phosphorylation of the mitogen-activated protein (MAP) kinases ERK (extracellular signal-regulated protein kinase) and p38 but not JNK (c-Jun N-terminal protein kinase). These effects were restricted to the infused dentate gyrus; no changes were observed in microdissected CA3 and CA1 regions. Local infusion of MEK (MAP kinase kinase) inhibitors (PD98059 and U0126) during BDNF delivery abolished BDNF-LTP and the associated ERK activation. Application of MEK inhibitor during established BDNF-LTP had no effect. Activation of MEK-ERK is therefore required for the induction, but not the maintenance, of BDNF-LTP. BDNF-LTP was further coupled to ERK-dependent phosphorylation of the transcription factor cAMP response element-binding protein. Finally, we investigated the expression of two immediate early genes, activity-regulated cytoskeleton-associated protein (Arc) and Zif268, both of which are required for generation of late, mRNA synthesis-dependent LTP. BDNF infusion resulted in selective upregulation of mRNA and protein for Arc. In situ hybridization showed that Arc transcripts are rapidly and extensively delivered to granule cell dendrites. U0126 blocked Arc upregulation in parallel with BDNF-LTP. The results support a model in which BDNF triggers long-lasting synaptic strengthening through MEK-ERK and selective induction of the dendritic mRNA species Arc.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor Induces Long-Term Potentiation in Intact Adult Hippocampus: Requirement for ERK Activation Coupled to CREB and Upregulation ofArcSynthesis

Ying

Futter²,

Rosenblum³

et al. 2002

J. Neurosci.

673

520

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“…The ERK1/2 pathway plays critical roles in cell proliferation, differentiation, and cell survival (Grewal et al, 1999;Impey et al, 1999;Agell et al, 2002;Cheung and Slack, 2004). Recent studies indicate that the NR2B subunit is coupled to ERK1/2 activation by Ras-guanylnucleotide releasing factor 1 (Krapivinsky et al, 2003).…”

Section: Differential Roles Of Nr2a and Nr2b In Nmdar-dependent Erk1/mentioning

confidence: 99%

Differential Roles of NR2A- and NR2B-Containing NMDA Receptors in Activity-Dependent Brain-Derived Neurotrophic Factor Gene Regulation and Limbic Epileptogenesis

Qian

He²,

Hu³

et al. 2007

J. Neurosci.

144

103

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Fleeting activation of NMDA receptors (NMDARs) induces long-term modification of synaptic connections and refinement of neuronal circuits, which may underlie learning and memory and contribute to pathogenesis of a diversity of neurological diseases, including epilepsy. Here, we found that NR2A and NR2B subunit-containing NMDARs were coupled to distinct intracellular signaling, resulting in differential BDNF expression and extracellular signal-regulated kinase 1/2 (ERK1/2) activation. Selective activation of NR2A-containing NMDARs increased BDNF gene expression. Activation of NR2B-containing NMDARs led to ERK1/2 phosphorylation. Furthermore, selectively blocking NR2A-containing NMDARs impaired epileptogenesis and the development of mossy fiber sprouting in the kindling and pilocarpine rat models of limbic epilepsy, whereas inhibiting NR2B-containing NMDARs had no effects in epileptogenesis and mossy fiber sprouting. Interestingly, blocking either NR2A- or NR2B-containing NMDARs decreased status epilepticus-induced neuronal cell death. The specific requirement of NR2A and its downstream signaling for epileptogenesis implicates attractive new targets for the development of drugs that prevent epilepsy in patients with brain injury.

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“…Activation of the MAPK pathway can promote either proliferation or differentiation, [79][80][81] as well as increase or decrease levels of cyclin D1 43,44,54 depending on signaling kinetics, cross talk with other pathways, and cellular history. Prolonged MAPK activation promotes cell cycle exit and differentiation in PC12 cells.…”

confidence: 99%

Progressive and Inhibitory Cell Cycle Proteins Act Simultaneously to Regulate Neurotrophin-mediated Proliferation and Maturation of Neuronal Precursors

Simpson

Moon²,

Kleman

et al. 2007

Cell Cycle

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ACKnowlEdGEMEntSWe thank Amy Palmer for helpful discussions and reading of the manuscript, and Susan McTeer for manuscript preparation. This work was supported by grants NIDCD RO3 DC005704 to P.J.S., NIDCD RO1 DC02979 and NINDS RO1 NS39657 to G.V.R. AbStRACtNeuronal stem cell expansion and differentiation is a process involving stages of proliferation and maturation governed by the sequential and combinatorial exposure of cells to extrinsic factors. The olfactory epithelium is an excellent model to investigate regulation of this process, as it undergoes neuronal replacement post-natally. We have shown that the neurotrophins NGF and BDNF sequentially promote proliferation of developing olfactory sensory neuronal precursors, although their kinetics of proliferation and cell fate outcomes differ. Interestingly, CNP inhibits this neurotrophin-induced proliferation and promotes the maturation of these precursors to their next developmental stage. Here, we investigate the mechanisms behind these actions. Both NGF and BDNF increase the expression of cyclin D1 and cyclin-dependent kinase 4 (cdk4), with temporal expression patterns that parallel the proliferation kinetics of their cellular targets. The timing of cyclin D1 expression reflects differences in the need for transcription and translation in early and late stage precursors. CNP inhibits neurotrophin-induced cyclin D1 expression, and induces the expression of different profiles of inhibitory cell cycle proteins, which are neurotrophin-specific and correlate with the attainment of different maturational cell fates. Inhibition of protein degradation reverses the effects of neurotrophins and CNP on cyclin D1 and inhibitor expression levels, respectively. These results suggest a model for cell cycle regulation that involves the simultaneous expression of progressive and inhibitory cell cycle regulatory proteins in response to both proliferation and differentiation agents, followed by selective degradation of these proteins, providing a mechanism for rapid and exquisite control of the cell cycle.

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Extracellular-signal-regulated kinase signalling in neurons

Cited by 520 publications

References 109 publications

Brain-Derived Neurotrophic Factor Induces Long-Term Potentiation in Intact Adult Hippocampus: Requirement for ERK Activation Coupled to CREB and Upregulation ofArcSynthesis

Brain-Derived Neurotrophic Factor Induces Long-Term Potentiation in Intact Adult Hippocampus: Requirement for ERK Activation Coupled to CREB and Upregulation ofArcSynthesis

Differential Roles of NR2A- and NR2B-Containing NMDA Receptors in Activity-Dependent Brain-Derived Neurotrophic Factor Gene Regulation and Limbic Epileptogenesis

Progressive and Inhibitory Cell Cycle Proteins Act Simultaneously to Regulate Neurotrophin-mediated Proliferation and Maturation of Neuronal Precursors

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