The role of CaMKII as an F-actin-bundling protein crucial for maintenance of dendritic spine structure.
Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine protein kinase critically involved in synaptic plasticity in the brain. It is highly concentrated in the postsynaptic density fraction, exceeding the amount of any other signal transduction molecules. Because kinase signaling can be amplified by catalytic reaction, why CaMKII exists in such a large quantity has been a mystery. Here, we provide biochemical evidence that CaMKII is capable of bundling F-actin through a stoichiometric interaction. Consistent with this evidence, in hippocampal neurons, RNAi-mediated down-regulation of CaMKII leads to a reduction in the volume of dendritic spine head that is mediated by F-actin dynamics. An overexpression of CaMKII slowed down the actin turnover in the spine head. This activity was associated with beta subunit of CaMKII in a manner requiring its actin-binding and association domains but not the kinase domain. This finding indicates that CaMKII serves as a central signaling molecule in both functional and structural changes during synaptic plasticity.
Okamoto
Ken-Ichi
K
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.
Narayanan
Radhakrishnan
R
Lee
Sang H
SH
Murata
Kazuyoshi
K
Hayashi
Yasunori
Y
D000199:Actins / Q000378:metabolism*; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism* / Q000648:ultrastructure; D006624:Hippocampus / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D009473:Neuronal Plasticity / Q000502:physiology*; D034622:RNA Interference; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism*
D000199:Actins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases