MAP kinase translocates into the nucleus of the presynaptic cell and is required for long-term facilitation in Aplysia.
Long-term facilitation of the sensory to motor synapse in Aplysia requires gene expression. While some transcription factors involved in long-term facilitation are phosphorylated by PKA, others lack PKA sites but contain MAP Kinase (MAPK) phosphorylation sites. We now show that MAPK translocates into the nucleus of the presynaptic but not the postsynaptic cell during 5-HT-induced long-term facilitation. The presynaptic nuclear translocation of MAPK is also triggered by elevations in intracellular cAMP. Injection of anti-MAPK antibodies or of MAPK Kinase inhibitors into the presynaptic cell blocks long-term facilitation, without affecting basal synaptic transmission or short-term facilitation. Thus, MAPK appears to be specifically recruited and necessary for the long-term form of facilitation. This mechanism for long-term plasticity may be quite general: cAMP also activated MAPK in mouse hippocampal neurons, suggesting that MAPK may play a role in hippocampal long-term potentiation.
Martin
K C
KC
Howard Hughes Medical Institute, Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Michael
D
D
Rose
J C
JC
Barad
M
M
Casadio
A
A
Zhu
H
H
Kandel
E R
ER
D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D005576:Colforsin / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D017774:Long-Term Potentiation / Q000502:physiology; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D008969:Molecular Sequence Data; D009473:Neuronal Plasticity / Q000502:physiology*; D009475:Neurons, Afferent / Q000201:enzymology; D010455:Peptides / Q000276:immunology; D017729:Presynaptic Terminals / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000494:pharmacology; D013569:Synapses; D009435:Synaptic Transmission
D004791:Enzyme Inhibitors; D005419:Flavonoids; D010455:Peptides; D005576:Colforsin; D012701:Serotonin; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one