Mitogen-Activated Protein Kinase Regulates Early Phosphorylation and Delayed Expression of Ca2+/Calmodulin-Dependent Protein Kinase II in Long-Term Potentiation

Activation of mitogen-activated protein kinase (MAPK) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) are required for numerous forms of neuronal plasticity, including long-term potentiation (LTP). We induced LTP in rat hippocampal area CA1 using theta-pulse stimulation (TPS) paired with β-adrenergic receptor activation [isoproterenol (ISO)], a protocol that may be particularly relevant to normal patterns of hippocampal activity during learning. This stimulation resulted in a transient phosphorylation of p42 MAPK, and the resulting LTP was MAPK dependent. In addition, CaMKII was regulated in two, temporally distinct ways after TPS–ISO: a transient rise in the fraction of phosphorylated CaMKII and a subsequent persistent increase in CaMKII expression. The increases in MAPK and CaMKII phosphorylation were strongly colocalized in the dendrites and cell bodies of CA1 pyramidal cells, and both the transient phosphorylation and delayed expression of CaMKII were prevented by inhibiting p42/p44 MAPK. These results establish a novel bimodal regulation of CaMKII by MAPK, which may contribute to both post-translational modification and increased gene expression.

[1]  M. Karin,et al.  Mammalian MAP kinase signalling cascades , 2001, Nature.

[2]  M. di Luca,et al.  Hippocampal Synaptic Plasticity Involves Competition between Ca2+/Calmodulin-Dependent Protein Kinase II and Postsynaptic Density 95 for Binding to the NR2A Subunit of the NMDA Receptor , 2001, The Journal of Neuroscience.

[3]  M. Kennedy,et al.  Densin-180 Forms a Ternary Complex with the α-Subunit of Ca2+/Calmodulin-Dependent Protein Kinase II and α-Actinin , 2001, The Journal of Neuroscience.

[4]  S. Shenolikar,et al.  Long-Term Potentiation Induced by θ Frequency Stimulation Is Regulated by a Protein Phosphatase-1-Operated Gate , 2000, The Journal of Neuroscience.

[5]  J. H. Connor,et al.  Molecular memory by reversible translocation of calcium/calmodulin-dependent protein kinase II , 2000, Nature Neuroscience.

[6]  Stefan Strack,et al.  Association of Calcium/Calmodulin-dependent Kinase II with Developmentally Regulated Splice Variants of the Postsynaptic Density Protein Densin-180* , 2000, The Journal of Biological Chemistry.

[7]  S. Grant,et al.  Proteomic analysis of NMDA receptor–adhesion protein signaling complexes , 2000, Nature Neuroscience.

[8]  M. Bear,et al.  Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity , 2000, Nature.

[9]  S. Davis,et al.  The MAPK/ERK Cascade Targets Both Elk-1 and cAMP Response Element-Binding Protein to Control Long-Term Potentiation-Dependent Gene Expression in the Dentate Gyrus In Vivo , 2000, The Journal of Neuroscience.

[10]  M. Kennedy,et al.  Identification of Proteins in the Postsynaptic Density Fraction by Mass Spectrometry , 2000, The Journal of Neuroscience.

[11]  G. Barrionuevo,et al.  The Extracellular Signal-Regulated Kinase Cascade Is Required for NMDA Receptor-Independent LTP in Area CA1 But Not Area CA3 of the Hippocampus , 2000, The Journal of Neuroscience.

[12]  R. Malinow,et al.  Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction. , 2000, Science.

[13]  J. Kaplan,et al.  CaMKII regulates the density of central glutamatergic synapses in vivo , 1999, Nature.

[14]  Eric R Kandel,et al.  ERK Plays a Regulatory Role in Induction of LTP by Theta Frequency Stimulation and Its Modulation by β-Adrenergic Receptors , 1999, Neuron.

[15]  K. Fukunaga,et al.  Differential Roles of Ca2+/Calmodulin-Dependent Protein Kinase II and Mitogen-Activated Protein Kinase Activation in Hippocampal Long-Term Potentiation , 1999, The Journal of Neuroscience.

[16]  S. Grewal,et al.  Extracellular-signal-regulated kinase signalling in neurons , 1999, Current Opinion in Neurobiology.

[17]  R. Nicoll,et al.  Long-term potentiation--a decade of progress? , 1999, Science.

[18]  M. Kennedy,et al.  Tetanic Stimulation Leads to Increased Accumulation of Ca2+/Calmodulin-Dependent Protein Kinase II via Dendritic Protein Synthesis in Hippocampal Neurons , 1999, The Journal of Neuroscience.

[19]  E. Nishida,et al.  Activation of the Protein Kinase ERK5/BMK1 by Receptor Tyrosine Kinases , 1999, The Journal of Biological Chemistry.

[20]  M. di Luca,et al.  αCaMKII binding to the C‐terminal tail of NMDA receptor subunit NR2A and its modulation by autophosphorylation , 1999, FEBS letters.

[21]  Daniel Johnston,et al.  Multiple forms of LTP in hippocampal CA3 neurons use a common postsynaptic mechanism , 1999, Nature Neuroscience.

[22]  J. Sweatt,et al.  The Mitogen-Activated Protein Kinase Cascade Couples PKA and PKC to cAMP Response Element Binding Protein Phosphorylation in Area CA1 of Hippocampus , 1999, The Journal of Neuroscience.

[23]  S. Gammeltoft,et al.  Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction , 1999, Molecular and Cellular Endocrinology.

[24]  T. Bliss,et al.  Single Synaptic Events Evoke NMDA Receptor–Mediated Release of Calcium from Internal Stores in Hippocampal Dendritic Spines , 1999, Neuron.

[25]  U. Bhalla,et al.  Emergent properties of networks of biological signaling pathways. , 1999, Science.

[26]  E. Quinlan,et al.  CPEB-Mediated Cytoplasmic Polyadenylation and the Regulation of Experience-Dependent Translation of α-CaMKII mRNA at Synapses , 1998, Neuron.

[27]  J. David Sweatt,et al.  The MAPK cascade is required for mammalian associative learning , 1998, Nature Neuroscience.

[28]  Shuang Huang,et al.  Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor , 1998, Nature.

[29]  Scott T. Wong,et al.  Cross Talk between ERK and PKA Is Required for Ca2+ Stimulation of CREB-Dependent Transcription and ERK Nuclear Translocation , 1998, Neuron.

[30]  Mark J. Thomas,et al.  Postsynaptic Complex Spike Bursting Enables the Induction of LTP by Theta Frequency Synaptic Stimulation , 1998, The Journal of Neuroscience.

[31]  R. Malinow,et al.  Calcium-Evoked Dendritic Exocytosis in Cultured Hippocampal Neurons. Part II: Mediation by Calcium/Calmodulin-Dependent Protein Kinase II , 1998, The Journal of Neuroscience.

[32]  P. Contreras,et al.  Immunolocalization of the mitogen‐activated protein kinases p42MAPK and JNK1, and their regulatory kinases MEK1 and MEK4, in adult rat central nervous system , 1998, The Journal of comparative neurology.

[33]  R. Colbran,et al.  Autophosphorylation-dependent Targeting of Calcium/ Calmodulin-dependent Protein Kinase II by the NR2B Subunit of theN-Methyl- d-aspartate Receptor* , 1998, The Journal of Biological Chemistry.

[34]  S. Shenolikar,et al.  Gating of CaMKII by cAMP-regulated protein phosphatase activity during LTP. , 1998, Science.

[35]  U. Frey,et al.  Synaptic tagging: implications for late maintenance of hippocampal long-term potentiation , 1998, Trends in Neurosciences.

[36]  M. Kennedy,et al.  A Synaptic Ras-GTPase Activating Protein (p135 SynGAP) Inhibited by CaM Kinase II , 1998, Neuron.

[37]  B. Morris,et al.  Increased expression of dendritic mRNA following the induction of long-term potentiation. , 1998, Brain research. Molecular brain research.

[38]  R. Huganir,et al.  SynGAP: a Synaptic RasGAP that Associates with the PSD-95/SAP90 Protein Family , 1998, Neuron.

[39]  Alcino J. Silva,et al.  Autophosphorylation at Thr286 of the alpha calcium-calmodulin kinase II in LTP and learning. , 1998, Science.

[40]  H. Cline,et al.  Stabilization of dendritic arbor structure in vivo by CaMKII. , 1998, Science.

[41]  M. Besson,et al.  In Vivo Expression and Regulation of Elk-1, a Target of the Extracellular-Regulated Kinase Signaling Pathway, in the Adult Rat Brain , 1998, The Journal of Neuroscience.

[42]  R. Levy,et al.  Cytosolic phospholipase A2 and its mode of activation in human neutrophils by opsonized zymosan. Correlation between 42/44 kDa mitogen-activated protein kinase, cytosolic phospholipase A2 and NADPH oxidase. , 1997, The Biochemical journal.

[43]  J. David Sweatt,et al.  A Requirement for the Mitogen-activated Protein Kinase Cascade in Hippocampal Long Term Potentiation* , 1997, The Journal of Biological Chemistry.

[44]  Sweatt Jd,et al.  A Requirement for the Mitogen-activated Protein Kinase Cascade in Hippocampal Long Term Potentiation , 1997 .

[45]  J. Lisman,et al.  Postsynaptic Inhibitors of Calcium/Calmodulin-Dependent Protein Kinase Type II Block Induction But Not Maintenance of Pairing-Induced Long-Term Potentiation , 1997, The Journal of Neuroscience.

[46]  K M Harris,et al.  Visualization of the Distribution of Autophosphorylated Calcium/Calmodulin-Dependent Protein Kinase II after Tetanic Stimulation in the CA1 Area of the Hippocampus , 1997, The Journal of Neuroscience.

[47]  R. Colbran,et al.  Differential Inactivation of Postsynaptic Density‐Associated and Soluble Ca2+/Calmodulin‐Dependent Protein Kinase II by Protein Phosphatases 1 and 2A , 1997, Journal of neurochemistry.

[48]  Jonathan A. Cooper,et al.  Mitogen‐activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2 , 1997, The EMBO journal.

[49]  U. Frey,et al.  Synaptic tagging and long-term potentiation , 1997, Nature.

[50]  R. V. Omkumar,et al.  Identification of a Phosphorylation Site for Calcium/Calmodulindependent Protein Kinase II in the NR2B Subunit of the N-Methyl-D-aspartate Receptor* , 1996, The Journal of Biological Chemistry.

[51]  K. Malik,et al.  Calcium/Calmodulin-dependent Protein Kinase IIα Mediates Activation of Mitogen-activated Protein Kinase and Cytosolic Phospholipase A2 in Norepinephrine-induced Arachidonic Acid Release in Rabbit Aortic Smooth Muscle Cells* , 1996, The Journal of Biological Chemistry.

[52]  J. Brosius,et al.  Translational Machinery in Dendrites of Hippocampal Neurons in Culture , 1996, Journal of Neuroscience.

[53]  E. Kandel,et al.  The 3'-untranslated region of CaMKII alpha is a cis-acting signal for the localization and translation of mRNA in dendrites. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[54]  B. Morris,et al.  Changes in hippocampal gene expression associated with the induction of long-term potentiation. , 1996, Brain research. Molecular brain research.

[55]  J. David Sweatt,et al.  Activation of p42 Mitogen-activated Protein Kinase in Hippocampal Long Term Potentiation* , 1996, The Journal of Biological Chemistry.

[56]  T. Teyler,et al.  Protein kinase and phosphatase activity regulate the form of synaptic plasticity expressed , 1996, Synapse.

[57]  M. Greenberg,et al.  Calcium Influx via the NMDA Receptor Induces Immediate Early Gene Transcription by a MAP Kinase/ERK-Dependent Mechanism , 1996, The Journal of Neuroscience.

[58]  Mark J. Thomas,et al.  Activity-Dependent β-Adrenergic Modulation of Low Frequency Stimulation Induced LTP in the Hippocampal CA1 Region , 1996, Neuron.

[59]  V. M. Pain.  Initiation of protein synthesis in eukaryotic cells. , 1996, European journal of biochemistry.

[60]  R. Iyengar,et al.  Postsynaptic CAMP pathway gates early LTP in hippocampal CA1 region , 1995, Neuron.

[61]  M. Loda,et al.  Cyclic Adenosine Monophosphate Can Convert Epidermal Growth Factor into a Differentiating Factor in Neuronal Cells (*) , 1995, The Journal of Biological Chemistry.

[62]  E. Krebs,et al.  The MAPK signaling cascade , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[63]  Dominique Muller,et al.  Increased Phosphorylation of Ca/Calmodulin-dependent Protein Kinase II and Its Endogenous Substrates in the Induction of Long Term Potentiation (*) , 1995, The Journal of Biological Chemistry.

[64]  C. Marshall,et al.  Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation , 1995, Cell.

[65]  J. Eberwine,et al.  On the nature and differential distribution of mRNAs in hippocampal neurites: implications for neuronal functioning. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[66]  T. Bliss,et al.  Spatial and temporal changes in signal transduction pathways during LTP , 1994, Neuron.

[67]  E. Kandel,et al.  Requirement of a critical period of transcription for induction of a late phase of LTP. , 1994, Science.

[68]  Lubert Stryer,et al.  Dual role of calmodulin in autophosphorylation of multifunctional cam kinase may underlie decoding of calcium signals , 1994, Neuron.

[69]  E. Kandel,et al.  Recruitment of long-lasting and protein kinase A-dependent long-term potentiation in the CA1 region of hippocampus requires repeated tetanization. , 1994, Learning & memory.

[70]  Mu-ming Poo,et al.  Turning of nerve growth cones induced by neurotransmitters , 1994, Nature.

[71]  R. Nicoll,et al.  The role of Ca2+ entry via synaptically activated NMDA receptors in the induction of long-term potentiation , 1993, Neuron.

[72]  E. Kandel,et al.  Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons. , 1993, Science.

[73]  T. Soderling,et al.  Phosphorylation and regulation of glutamate receptors by calcium/calmodulin-dependent protein kinase II , 1993, Nature.

[74]  T. Bliss,et al.  A synaptic model of memory: long-term potentiation in the hippocampus , 1993, Nature.

[75]  J. Eberwine,et al.  Stimulus-induced coordinate changes in mRNA abundance in single postsynaptic hippocampal CA1 neurons , 1992, Neuron.

[76]  T. Soderling,et al.  Regulatory Properties of Calcium/Calmodulin‐Dependent Protein Kinase II in Rat Brain Postsynaptic Densities , 1989, Journal of neurochemistry.

[77]  K. Fukunaga,et al.  Differential roles of Ca(2+)/calmodulin-dependent protein kinase II and mitogen-activated protein kinase activation in hippocampal long-term potentiation. , 1999, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[78]  J. Sweatt,et al.  Activation of p 42 Mitogen-activated Protein Kinase in Hippocampal Long Term Potentiation * , 1996 .

[79]  H. Schulman,et al.  Neuronal Ca2+/calmodulin-dependent protein kinases. , 1992, Annual review of biochemistry.

[80]  J P Reboud,et al.  [Initiation of protein synthesis in eukaryotic cells]. , 1969, Comptes rendus hebdomadaires des seances de l'Academie des sciences. Serie D: Sciences naturelles.