Role of ERK signaling in activity-dependent modifications of histone proteins.
It is well-established that neuronal intracellular signaling governed by the extracellular signal-regulated kinase (ERK/MAPK) plays a crucial role in long-term adaptive changes that occur during cognitive processes. ERK is a downstream component of a conserved signaling module that is activated by the serine/threonine kinase, Raf, which activates the MAPK/ERK kinase (MEK)1/2 protein kinases, which, in turn, activate ERK1/2. This signaling pathway has been reported to be activated in numerous physiological conditions due to a variety of stimuli, ranging from the activation of ionotropic glutamatergic receptors to metabotropic dopaminergic receptors and neurotrophin receptors. Interestingly, activated ERK can have early and late downstream effects at both the nuclear and synaptic levels. Locally, ERK signaling results in transient changes in the efficacy of synaptic transmission by modifying both pre- and post-synaptic targets. Once translocated into the nucleus, ERK signaling may control transcription by targeting several different regulators of gene expression such as transcription factors and histone proteins. ERK function is considered fundamental in processes such as long-term memory storage and drug addiction, by means of its role in activity-dependent epigenetic modifications that occur in the brain. In this review, we summarize the current understanding of ERK action in the neuroepigenetic processes underlying physiological responses, cognitive processes and drug addiction.
University of Turin, Department of Neuroscience, C.so M. D'Azeglio 52, 10126 Turin, Italy.
Alessandro
A
Ciccarelli
University of Turin, Department of Neuroscience, C.so M. D'Azeglio 52, 10126 Turin, Italy; National Institute of Neuroscience-Italy, C.so M. D'Azeglio 52, 10126 Turin, Italy. Electronic address: maurizio.giustetto@unito.it.
Maurizio
M
Giustetto
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006657:Histones / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008954:Models, Biological; D009294:Narcotics / Q000633:toxicity; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009293:Opioid-Related Disorders / Q000201:enzymology / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D006657:Histones; D009294:Narcotics; D009419:Nerve Tissue Proteins
Drug addiction; Histones; Learning and memory; MAP kinase; MeCP2; Nucleus accumbens; Synaptic plasticity