TY - JOUR
T1 - Mitogen-activated protein kinase regulates early phosphorylation and delayed expression of Ca2+/calmodulin-dependent protein kinase II in long-term potentiation
AU - Giovannini, Maria Grazia
AU - Blitzer, Robert D.
AU - Wong, Tony
AU - Asoma, Kichiemon
AU - Tsokas, Panayiotis
AU - Morrison, John H.
AU - Iyengar, Ravi
AU - Landau, Emmanuel M.
PY - 2001/9/15
Y1 - 2001/9/15
N2 - Activation of mitogen-activated protein kinase (MAPK) and Ca2+/calmodulin 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.
AB - Activation of mitogen-activated protein kinase (MAPK) and Ca2+/calmodulin 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.
KW - Ca/calmodulin-dependent protein kinase II
KW - Erk
KW - Long-term potentiation
KW - Mitogen-activated protein kinase
KW - Phosphorylation
KW - Protein synthesis
KW - Rat hippocampus
KW - β-adrenergic receptors
UR - http://www.scopus.com/inward/record.url?scp=0035885153&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.21-18-07053.2001
DO - 10.1523/jneurosci.21-18-07053.2001
M3 - Article
C2 - 11549715
AN - SCOPUS:0035885153
SN - 0270-6474
VL - 21
SP - 7053
EP - 7062
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 18
ER -