Induction of spine growth and synapse formation by regulation of the spine actin cytoskeleton.
We explored the relationship between regulation of the spine actin cytoskeleton, spine morphogenesis, and synapse formation by manipulating expression of the actin binding protein NrbI and its deletion mutants. In pyramidal neurons of cultured rat hippocampal slices, NrbI is concentrated in dendritic spines by binding to the actin cytoskeleton. Expression of one NrbI deletion mutant, containing the actin binding domain, dramatically increased the density and length of dendritic spines with synapses. This hyperspinogenesis was accompanied by enhanced actin polymerization and spine motility. Synaptic strengths were reduced to compensate for extra synapses, keeping total synaptic input per neuron constant. Our data support a model in which synapse formation is promoted by actin-powered motility.
Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Karen
K
Zito
Graham
G
Knott
Gordon M G
GM
Shepherd
Shirish
S
Shenolikar
Karel
K
Svoboda
D000199:Actins / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D003599:Cytoskeleton / Q000502:physiology*; D003712:Dendrites / Q000502:physiology* / Q000648:ultrastructure; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D008854:Microscopy, Electron; D008959:Models, Neurological; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009473:Neuronal Plasticity; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000166:cytology*; D051381:Rats; D017385:Sequence Homology; D013569:Synapses / Q000502:physiology / Q000648:ultrastructure; D014162:Transfection; D000099273:Neurabins
D000199:Actins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D000099273:Neurabins