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. 2011 May;4(3):281-3.
doi: 10.4161/cib.4.3.14766.

Fine-tuning MAPK signaling in the brain: The role of MKP-1

Freddy Jeanneteau  1 , Katrin Deinhardt
Affiliations

Fine-tuning MAPK signaling in the brain: The role of MKP-1

Freddy Jeanneteau et al. Commun Integr Biol. 2011 May.

Abstract

Mitogen-activated protein kinase (MAPK) signaling influences a variety of neuronal properties, including structural characteristics such as spine density, and physiological features like long-term potentiation. Spatiotemporal control of MAPK signaling is crucial to generate specific changes in neuronal physiology. However, while many studies have concentrated on the activation of MAPK signaling by trophic factors such as BDNF and neuronal activity, the mechanisms that lead to its termination have not been well described. Two recent reports begin to address this question by focusing on the role of the MAPK phosphatase, MKP-1, in neuronal function. The first study provides a cellular mechanism underlying MKP-1 action in the brain.1 The second study describes potential roles of MKP-1 during stress and major depression.2.

Keywords: arborization; cytoskeleton; disease; misexpression; neurotrophin; phosphatase; signaling.

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Figures

Figure 1
Figure 1
Control of MKP-1 levels. (A) Baseline expression of MKP-1 is low, but highly inducible by sensory stimuli, neuronal activity and trophic factors such as BDNF. Once expressed, MKP-1 is unstable with a turnover <1 h. When phosphorylated by neuronal activity or BDNF, MKP-1 stability extends to >8 h. As a consequence, MAPK signaling is shaped accordingly to MKP-1 levels. (B) The mechanisms that regulate MKP-1 levels involve protein kinases and ubiquitin ligases. Abnormal expression of MKP-1 is a hallmark of several disorders, such as stress and depression.
Figure 2
Figure 2
Titration of MKP-1 levels determines the physiological outcome. (A) Scheme summarizing the effects of MKP-1 on morphological plasticity. Loss of mkp-1 prevents activity-dependent and BDNF-induced morphological plasticity of the axon compared to wildtype controls. However, neuronal morphology is indistinguishable between the two genotypes under baseline conditions. Transient induction of MKP-1 mirrors the effects of BDNF and neuronal activity on axon branching, whereas prolonged expression prevents axon growth. (B) Ectopic expression of MKP-1 disrupts axonal growth at any stage of development. Length of the longest neurite per cell (mean ± SEM). Numbers in bars indicate the number of cells analyzed. ***p < 0.01, t test, n= 3 independent experiments. n.s., not significant.
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References

    1. Jeanneteau F, Deinhardt K, Miyoshi G, Bennett AM, Chao MV. The MAP kinase phosphatase MKP-1 regulates BDNF-induced axon branching. Nat Neurosci. 2010;13:1373–1379. - PMC - PubMed
    1. Duric V, Banasr M, Licznerski P, Schmidt HD, Stockmeier CA, Simen AA, et al. A negative regulator of MAP kinase causes depressive behavior. Nat Med. 2010;16:1328–1332. - PMC - PubMed
    1. Liu Y, Shepherd EG, Nelin LD. MAPK phosphatases—regulating the immune response. Nat Rev Immunol. 2007;7:202–212. - PubMed
    1. Boutros T, Chevet E, Metrakos P. Mitogen-activated protein (MAP) kinase/MAP kinase phosphatase regulation: roles in cell growth, death and cancer. Pharmacol Rev. 2008;60:261–310. - PubMed
    1. Keyse SM, Emslie EA. Oxidative stress and heat shock induce a human gene encoding a protein-tyrosine phosphatase. Nature. 1992;359:644–647. - PubMed

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