Brain-Derived Neurotrophic Factor and Epidermal Growth Factor Activate Neuronal m-Calpain via Mitogen-Activated Protein Kinase-Dependent Phosphorylation

Zadran, Sohila; Jourdi, Hussam; Rostamiani, Karoline; Qin, Qingyu; Bi, Xiaoning; Baudry, Michel

doi:10.1523/jneurosci.5120-09.2010

Cited by 111 publications

(112 citation statements)

References 47 publications

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“…Thus, it has been shown that calpain 2, but not calpain 1, was activated by ERKmediated phosphorylation under certain experimental conditions (59,60,61). Because the ERK signal transduction pathway is highly activated in the presence of Aβ in mature central neurons, it is possible that this mechanism could play a role in the generation of the 17-kDa tau in AD 20,22).…”

Section: Discussionmentioning

confidence: 99%

Calpain-Mediated Tau Cleavage: A Mechanism Leading to Neurodegeneration Shared by Multiple Tauopathies

Ferreira

Bigio

2011

Mol Med

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Tau dysfunction has been associated with a host of neurodegenerative diseases called tauopathies. These diseases share, as a common pathological hallmark, the presence of intracellular aggregates of hyperphosphorylated tau in affected brain areas. Aside from tau hyperphosphorylation, little is known about the role of other posttranslational modifications in tauopathies. Recently, we obtained data suggesting that calpain-mediated tau cleavage leading to the generation of a neurotoxic tau fragment might play an important role in Alzheimer's disease. In the current study, we assessed the presence of this tau fragment in several tauopathies. Our results show high levels of the 17-kDa tau fragment and enhanced calpain activity in the temporal cortex of AD patients and in brain samples obtained from patients with other tauopathies. In addition, our data suggest that this fragment could partially inhibit tau aggregation. Conversely, tau aggregation might prevent calpain-mediated cleavage, establishing a feedback circuit that might lead to the accumulation of this toxic tau fragment. Collectively, these data suggest that the mechanism underlying the generation of the 17-kDa neurotoxic tau fragment might be part of a conserved pathologic process shared by multiple tauopathies.

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Section: Discussionmentioning

confidence: 99%

Calpain-Mediated Tau Cleavage: A Mechanism Leading to Neurodegeneration Shared by Multiple Tauopathies

Ferreira

Bigio

2011

Mol Med

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“…Studies performed in hippocampal slices from adult rats showed that BDNF mediates the thetaburst stimulation-induced increase in actin polymerization in dendritic spines, through regulation of p21-activated kinase (PAK) and ADF (actin-depolymerizing factor)/cofilin ). An increase in actin polymerization in spines may also arise from activation of m-calpain through ERK-dependent phosphorylation, as shown in cultured neurons (Zadran et al, 2010). F-actin polymerization in spines plays a key role in LTP maintenance in vivo (Fukazawa et al, 2003) and, therefore, these alterations may underlie some of the effects of BDNF in long-term synaptic potentiation.…”

Section: Bdnf and Spine Plasticitymentioning

confidence: 99%

BDNF-induced local protein synthesis and synaptic plasticity

2014

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a b s t r a c tBrain-derived neurotrophic factor (BDNF) is an important regulator of synaptic transmission and longterm potentiation (LTP) in the hippocampus and in other brain regions, playing a role in the formation of certain forms of memory. The effects of BDNF in LTP are mediated by TrkB (tropomyosin-related kinase B) receptors, which are known to be coupled to the activation of the Ras/ERK, phosphatidylinositol 3-kinase/Akt and phospholipase C-g (PLC-g) pathways. The role of BDNF in LTP is best studied in the hippocampus, where the neurotrophin acts at pre-and post-synaptic levels. Recent studies have shown that BDNF regulates the transport of mRNAs along dendrites and their translation at the synapse, by modulating the initiation and elongation phases of protein synthesis, and by acting on specific miRNAs. Furthermore, the effect of BDNF on transcription regulation may further contribute to long-term changes in the synaptic proteome. In this review we discuss the recent progress in understanding the mechanisms contributing to the short-and long-term regulation of the synaptic proteome by BDNF, and the role in synaptic plasticity, which is likely to influence learning and memory formation.This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'.

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“…In addition to activity-induced elevation in intracellular Ca 2ϩ , calpain is also activated by BDNF signaling (Zadran et al, 2010a). Seizure-induced upregulation of BDNF/TrkB signaling (Binder et al, 2001;Rivera et al, 2002) and activity-dependent endogenous release as well as exogenous application of BDNF (Rivera et al, 2002(Rivera et al, , 2004Wake et al, 2007), all have been shown to downregulate KCC2 protein and function, demonstrating a critical role for TrkB activation in activity-dependent downregulation of KCC2.…”

Section: Enhanced Degradation Of Kcc2 Leads To Fast Changes In Gabaermentioning

confidence: 99%

“…4) indicate that a fraction of KCC2 is resistant to calpain within the time window of the present experiments. Curiously, BDNF-calpain signaling has been proposed to regulate spine plasticity (Zadran et al, 2010a). Since spines are known to express high levels of KCC2 (cf.…”

Section: Enhanced Degradation Of Kcc2 Leads To Fast Changes In Gabaermentioning

confidence: 99%

Activity-Dependent Cleavage of the K-Cl Cotransporter KCC2 Mediated by Calcium-Activated Protease Calpain

et al. 2012

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The K-Cl cotransporter KCC2 plays a crucial role in neuronal chloride regulation. In mature central neurons, KCC2 is responsible for the low intracellular Cl Ϫ concentration ([Cl Ϫ ] i ) that forms the basis for hyperpolarizing GABA A receptor-mediated responses. Fast changes in KCC2 function and expression have been observed under various physiological and pathophysiological conditions. Here, we show that the application of protein synthesis inhibitors cycloheximide and emetine to acute rat hippocampal slices have no effect on total KCC2 protein level and K-Cl cotransporter function. Furthermore, blocking constitutive lysosomal degradation with leupeptin did not induce significant changes in KCC2 protein levels. These findings indicate a low basal turnover rate of the total KCC2 protein pool. In the presence of the glutamate receptor agonist NMDA, the total KCC2 protein level decreased to about 30% within 4 h, and this effect was blocked by calpeptin and MDL-28170, inhibitors of the calcium-activated protease calpain. Interictal-like activity induced by incubation of hippocampal slices in an Mg 2ϩ -free solution led to a fast reduction in KCC2-mediated Cl Ϫ transport efficacy in CA1 pyramidal neurons, which was paralleled by a decrease in both total and plasmalemmal KCC2 protein. These effects were blocked by the calpain inhibitor MDL-28170. Taken together, these findings show that calpain activation leads to cleavage of KCC2, thereby modulating GABAergic signaling.

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Brain-Derived Neurotrophic Factor and Epidermal Growth Factor Activate Neuronal m-Calpain via Mitogen-Activated Protein Kinase-Dependent Phosphorylation

Cited by 111 publications

References 47 publications

Calpain-Mediated Tau Cleavage: A Mechanism Leading to Neurodegeneration Shared by Multiple Tauopathies

Calpain-Mediated Tau Cleavage: A Mechanism Leading to Neurodegeneration Shared by Multiple Tauopathies

BDNF-induced local protein synthesis and synaptic plasticity

Activity-Dependent Cleavage of the K-Cl Cotransporter KCC2 Mediated by Calcium-Activated Protease Calpain

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