Myosin II ATPase activity mediates the long-term potentiation-induced exodus of stable F-actin bound by drebrin A from dendritic spines

Toshiyuki Mizui; Yuko Sekino; Hiroyuki Yamazaki; Yuta Ishizuka; Hideto Takahashi; Nobuhiko Kojima; Masami Kojima; Tomoaki Shirao

doi:10.1371/journal.pone.0085367

Myosin II ATPase activity mediates the long-term potentiation-induced exodus of stable F-actin bound by drebrin A from dendritic spines

PLoS One. 2014 Jan 22;9(1):e85367. doi: 10.1371/journal.pone.0085367. eCollection 2014.

Authors

Toshiyuki Mizui¹, Yuko Sekino², Hiroyuki Yamazaki³, Yuta Ishizuka³, Hideto Takahashi³, Nobuhiko Kojima³, Masami Kojima⁴, Tomoaki Shirao³

Affiliations

¹ 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.
² 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.
³ Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
⁴ 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.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actins / metabolism*
Adenosine Triphosphatases / metabolism
Animals
Bicuculline / pharmacology
Calcium / metabolism
Cells, Cultured
Dendritic Spines / drug effects
Dendritic Spines / metabolism*
Dendritic Spines / physiology
Female
GABA-A Receptor Antagonists / pharmacology
Glutamic Acid / pharmacology
Glycine / pharmacology
Hippocampus / cytology
Long-Term Potentiation / drug effects
Long-Term Potentiation / physiology*
Microscopy, Fluorescence
Myosin Type II / metabolism*
Neurons / cytology
Neurons / metabolism
Neuropeptides / metabolism*
Phosphorylation
Pregnancy
Protein Binding
Rats
Rats, Wistar
Receptors, N-Methyl-D-Aspartate / metabolism
Tetrodotoxin / pharmacology
Time-Lapse Imaging

Substances

Actins
GABA-A Receptor Antagonists
Neuropeptides
Receptors, N-Methyl-D-Aspartate
drebrins
Glutamic Acid
Tetrodotoxin
Adenosine Triphosphatases
Myosin Type II
Calcium
Glycine
Bicuculline

Grants and funding

This work was supported by Grants-in-Aid for Scientific Research (16300117, 19200029) and on Priority Areas - Elucidation of neural network function in the brain - from the Ministry of Education, Culture, Sports, Science and Technology of Japan (20021002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.