Myosin II ATPase activity mediates the long-term potentiation-induced exodus of stable F-actin bound by drebrin A from dendritic spines.
The neuronal actin-binding protein drebrin A forms a stable structure with F-actin in dendritic spines. NMDA receptor activation causes an exodus of F-actin bound by drebrin A (DA-actin) from dendritic spines, suggesting a pivotal role for DA-actin exodus in synaptic plasticity. We quantitatively assessed the extent of DA-actin localization to spines using the spine-dendrite ratio of drebrin A in cultured hippocampal neurons, and found that (1) chemical long-term potentiation (LTP) stimulation induces rapid DA-actin exodus and subsequent DA-actin re-entry in dendritic spines, (2) Ca(2+) influx through NMDA receptors regulates the exodus and the basal accumulation of DA-actin, and (3) the DA-actin exodus is blocked by myosin II ATPase inhibitor, but is not blocked by myosin light chain kinase (MLCK) or Rho-associated kinase (ROCK) inhibitors. These results indicate that myosin II mediates the interaction between NMDA receptor activation and DA-actin exodus in LTP induction. Furthermore, myosin II seems to be activated by a rapid actin-linked mechanism rather than slow MLC phosphorylation. Thus the myosin-II mediated DA-actin exodus might be an initial event in LTP induction, triggering actin polymerization and spine enlargement.
Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan ; Bio-interface Research Group, Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka, Japan.
Toshiyuki
T
Mizui
Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan ; Core Research for Evolution Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama, Japan.
Yuko
Y
Sekino
Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Hiroyuki
H
Yamazaki
Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Yuta
Y
Ishizuka
Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Hideto
H
Takahashi
Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Nobuhiko
N
Kojima
Core Research for Evolution Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama, Japan ; Bio-interface Research Group, Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka, Japan.
Masami
M
Kojima
Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Tomoaki
T
Shirao
D000199:Actins / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D005260:Female; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008856:Microscopy, Fluorescence; D024462:Myosin Type II / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D010766:Phosphorylation; D011247:Pregnancy; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D059008:Time-Lapse Imaging
D000199:Actins; D058787:GABA-A Receptor Antagonists; D009479:Neuropeptides; D016194:Receptors, N-Methyl-D-Aspartate; C053386:drebrins; D018698:Glutamic Acid; D013779:Tetrodotoxin; D000251:Adenosine Triphosphatases; D024462:Myosin Type II; D002118:Calcium; D005998:Glycine; D001640:Bicuculline