The dynamic turnover and functional roles of alpha-actinin in dendritic spines.
Excitatory synapses are located on actin-rich protrusions known as dendritic spines. alpha-Actinin is an actin binding protein enriched in the postsynaptic density (PSD) of excitatory synapses. Because it also binds to NMDA receptors and other PSD components, alpha-actinin has been proposed to link NMDA receptors and the PSD to the underlying actin cytoskeleton of the dendritic spine. Although alpha-actinin has been implicated in modulation of NMDA receptor activity, the cell biological function of alpha-actinin in neurons is unknown. We report here that alpha-actinin is concentrated in spines. Both the actin binding domain and the spectrin repeat region (which interacts with NMDA receptors) of alpha-actinin2 are required for spine targeting. In live imaging experiments, Venus-tagged alpha-actinin2 in dendritic spines showed faster turnover than PSD-95, as determined by fluorescent recovery after photobleaching (FRAP), and individual spines often showed marked fluctuations in alpha-actinin content over a time-scale of minutes. Overexpression of alpha-actinin2 increased the length and density of dendritic protrusions in cultured hippocampal neurons, an effect that requires the actin binding domain and the spectrin repeats of alpha-actinin. These results suggest that alpha-actinin regulates spine morphology and density.
The Picower Center for Learning and Memory, RIKEN-MIT Neuroscience Research Center, Howard Hughes Medical Institute, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Room E18-215, Cambridge, MA 02139-4301, USA.
Terunaga
T
Nakagawa
John A
JA
Engler
Morgan
M
Sheng
D000185:Actinin / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology* / Q000648:ultrastructure; D006624:Hippocampus; D007700:Kinetics; D018613:Microscopy, Confocal; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D016133:Polymerase Chain Reaction; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D016194:Receptors, N-Methyl-D-Aspartate; D000185:Actinin