Ras Protein Activation Is a Key Event in Activity-dependent Survival of Cerebellar Granule Neurons

Xifró, Xavier; Miñano-Molina, Alfredo J.; Saura, Carlos A.; Rodríguez‐Álvarez, José

doi:10.1074/jbc.m113.536375

Cited by 11 publications

(12 citation statements)

References 45 publications

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“…Slice Pharmacology-As described previously (43,44), neostriatum from 10-to 12-week-old wild-type male C57BL/6 mice was acutely microdissected from 350-m coronal slices and equilibrated for 30 min with adenosine deaminase (10 g/ml) in Krebs-HCO 3 Ϫ buffer (124 mM NaCl, 4 mM KCl, 26 mM NaHCO 3 , 1.5 mM CaCl 2 , 1.25 mM KH 2 PO 4 , 1.5 mM MgSO 4 , and 10 mM D-glucose (pH 7.4)) oxygenated with 95% O 2 /5% CO 2 followed by another 30 min incubation in fresh Krebs-HCO 3 Ϫ buffer. Some striatal slices were pre-incubated for 1 h in Krebs buffer plus dimethyl sulfoxide vehicle, 40 M U0126, 50 M CP681301, and/or 200 nM or 1 M okadaic acid.…”

Section: Methodsmentioning

confidence: 99%

“…MS analysis was performed on a QSTAR Pulsar I quadrupole time of flight tandem mass spectrometer (Applied Biosystems/ MDS SCIEX) equipped with a nanoelectrospray ion source (MDS Proteomics, Odense, Denmark). For precursor ion scanning, the instrument was set in negative ion mode to detect the PO 3 Ϫ fragment ion at m/z Ϫ79. After data acquisition, the instrument was switched to positive ion mode, and the phosphopeptide sequence and site of phosphorylation were determined by nanoelectrospray-QSTAR Pulsar I quadrupole time of flight MS/MS.…”

Section: Methodsmentioning

confidence: 99%

“…These kinases are critical in the transduction of receptor activation signals that affect many cellular functions, including gene transcription and translation, cell differentiation and survival, and modulation of cell structure and metabolism. Within the CNS, ERK signaling is essential to brain development and neurite outgrowth (1), neuronal survival (2,3), and synaptic plasticity (4,5). ERK activation is necessary for the consolidation and reconsolidation of hippocampus-dependent memory (6).…”

mentioning

confidence: 99%

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Regulation of ERK Kinase by MEK1 Kinase Inhibition in the Brain

Tassin¹,

Benavides

Plattner³

et al. 2015

Journal of Biological Chemistry

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Background: ERK/MAPK signaling is important in brain function. Results: MEK1 is inhibited by phosphorylation at Thr-292/286 by Cdk5, ERK, and Cdk1. These mechanisms are regulated by striatal glutamate and dopamine neurotransmission and acute stress in vivo. Conclusion: Excitatory and metabotropic neurotransmission converge on MEK1 regulation. Significance: A greater understanding of MEK1/ERK signaling provides insights into brain function, disease, and potential treatment strategies.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Regulation of ERK Kinase by MEK1 Kinase Inhibition in the Brain

Tassin¹,

Benavides

Plattner³

et al. 2015

Journal of Biological Chemistry

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“…Activation of TRPC leads to trans-sarcolemmal Ca 2+ influx to directly increase the intracellular Ca 2+ concentration; it can also lead to trans-sarcolemmal Na + influx to indirectly increase the intracellular Ca 2+ concentration [7]. There is evidence that, in cerebellar granule cells cultured in vitro , when TRPC3 and TRPC6 channels are opened, activation of the Ca 2+ /Ras/MEK/ERK and Ca 2+ /CaM/CaMK signaling pathways can phosphorylate cAMP-response element binding protein (CREB) and increase its transcriptional activity, thereby promoting the survival of neurons [8]. …”

Section: Introductionmentioning

confidence: 99%

TRPC3 Overexpression Promotes the Progression of Inflammation-Induced Preterm Labor and Inhibits T Cell Activation

Chen¹,

Dongming²,

Chen³

et al. 2018

Cell Physiol Biochem

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Background/Aims: To detect the expression of the TRPC3 channel protein in the tissues of women experiencing preterm labor and investigate its interaction with T lymphocytes, providing a theoretical basis for the clinical prevention of threatened preterm labor and the development of drug-targeted therapy. Methods: Forty-seven women experiencing preterm labor and 47 women experiencing normal full-term labor were included in this study. All included women underwent delivery via cesarean section; uterine samples were obtained at delivery. The expression of TRPC3 in uterine tissue was detected by immunohistochemistry, real-time quantitative reverse transcription-PCR, and western blot assay. Activation of T lymphocytes in peripheral blood and uterine tissue were detected by flow cytometry. A TRPC3^-/- mouse model of inflammation-induced preterm labor was established; expression of TRPC3, Cav3.1, and Cav3.2 were analyzed in mouse uterine tissue. Activation of T lymphocytes in female mouse and human peripheral blood samples was determined using flow cytometry. Results: In women experiencing preterm labor, expression of TRPC3 and the Cav3.1 and Cav3.2 proteins was significantly increased; in addition, the percentage of CD3⁺, CD4⁺, and CD8⁺ T cells in peripheral blood was significantly decreased. TRPC3 knockout significantly delayed the occurrence of preterm labor in mice. The muscle tension of ex vivo uterine strips was lower, Cav3.1 and Cav3.2 protein expression was lower, and the percentage of CD8⁺ T lymphocytes was significantly increased in wild-type mice subjected to an inflammation-induced preterm labor than in wild-type mice experiencing normal full-term labor. Conclusion: TRPC3 is closely related to the initiation of labor. TRPC3 relies on Cav3.1 and Cav3.2 proteins to inhibit inflammation-induced preterm labor by inhibiting the activation of T cells, in particular CD8⁺ T lymphocytes.

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“…18,28 We recently reported that the survival role of PI3K/Akt and ERK pathways in CGNs depends on the small G proteins acting upstream. 30 We demonstrated that both pathways are involved in NMDA-mediated neuroprotection when they are activated by Ras. In contrast, the stimulation of the ERK pathway by other members of the small G proteins family, such as Rap1, is not sufficient to promote protection.…”

Section: Molecular Pathways Related To the Neuroprotection Of Cgnsmentioning

confidence: 99%

Delineating the Factors and Cellular Mechanisms Involved in the Survival of Cerebellar Granule Neurons

Xifró

Rodríguez‐Álvarez

2015

Cerebellum

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Cerebellar granule neurons (CGNs) constitute the most abundant neuronal population in the mammalian brain. Their postnatal generation and the feasibility to induce their apoptotic death in vitro make them an excellent model to study the effect of several neurotransmitters and neurotrophins. Here, we first review which factors are involved in the generation and proliferation of CGNs in the external granule layer (EGL) and in the regulation of their differentiation and migration to internal granule layer (IGL). Special attention was given to the role of several neurotrophins and the NMDA subtype of glutamate receptor. Then, using the paradigm of potassium deprivation in cultured CGNs, we address several extracellular factors that promote the survival of CGNs, with particular emphasis on the cellular mechanisms. The role of specific protein kinases leading to the regulation of transcription factors and recent data involving the small G protein family is also discussed. Finally, the participation of some members of Bcl-2 family and the inhibition of mitochondria-related apoptotic pathway is also considered. Altogether, these studies evidence that CGNs are a key model to understand the development and the survival of neuronal populations.

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Ras Protein Activation Is a Key Event in Activity-dependent Survival of Cerebellar Granule Neurons

Cited by 11 publications

References 45 publications

Regulation of ERK Kinase by MEK1 Kinase Inhibition in the Brain

Regulation of ERK Kinase by MEK1 Kinase Inhibition in the Brain

TRPC3 Overexpression Promotes the Progression of Inflammation-Induced Preterm Labor and Inhibits T Cell Activation

Delineating the Factors and Cellular Mechanisms Involved in the Survival of Cerebellar Granule Neurons

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