A Temporary Gating of Actin Remodeling during Synaptic Plasticity Consists of the Interplay between the Kinase and Structural Functions of CaMKII.
The structural modification of dendritic spines plays a critical role in synaptic plasticity. CaMKII is a pivotal molecule involved in this process through both kinase-dependent and independent structural functions, but the respective contributions of these two functions to the synaptic plasticity remain unclear. We demonstrate that the transient interplay between the kinase and structural functions of CaMKII during the induction of synaptic plasticity temporally gates the activity-dependent modification of the actin cytoskeleton. Inactive CaMKII binds F-actin, thereby limiting access of actin-regulating proteins to F-actin and stabilizing spine structure. CaMKII-activating stimuli trigger dissociation of CaMKII from F-actin through specific autophosphorylation reactions within the F-actin binding region and permits F-actin remodeling by regulatory proteins followed by reassociation and restabilization. Blocking the autophosphorylation impairs both functional and structural plasticity without affecting kinase activity. These results underpin the importance of the interplay between the kinase and structural functions of CaMKII in defining a time window permissive for synaptic plasticity.
Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan.
Karam
K
Kim
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada.
Gurpreet
G
Lakhanpal
Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Program in Molecular Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Hsiangmin E
HE
Lu
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada.
Mustafa
M
Khan
Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan.
Akio
A
Suzuki
RIKEN-MIT Neuroscience Research Center, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Mariko Kato
MK
Hayashi
RIKEN-MIT Neuroscience Research Center, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Radhakrishnan
R
Narayanan
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada; Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Thomas T
TT
Luyben
The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan.
Tomoki
T
Matsuda
The Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan.
Takeharu
T
Nagai
Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Program in Molecular Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Thomas A
TA
Blanpied
Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan; RIKEN-MIT Neuroscience Research Center, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Brain and Body System Science Institute, Saitama University, Saitama 338-8570, Japan; School of Life Science, South China Normal University, Guangzhou 510631, China. Electronic address: yhayashi@brain.riken.jp.
Yasunori
Y
Hayashi
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada; RIKEN-MIT Neuroscience Research Center, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Molecular Genetics, Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada. Electronic address: okamoto@lunenfeld.ca.
Kenichi
K
Okamoto
D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D049229:Dendritic Spines / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D009924:Organ Culture Techniques; D011485:Protein Binding / Q000502:physiology; D051381:Rats
D000199:Actins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2