Rapid turnover of actin in dendritic spines and its regulation by activity.
Dendritic spines are motile structures that contain high concentrations of filamentous actin. Using hippocampal neurons expressing fluorescent actin and the method of fluorescence recovery after photobleaching, we found that 85 +/- 2% of actin in the spine was dynamic, with a turnover time of 44.2 +/- 4.0 s. The rapid turnover is not compatible with current models invoking a large population of stable filaments and static coupling of filaments to postsynaptic components. Low-frequency stimulation known to induce long-term depression in these neurons stabilized nearly half the dynamic actin in the spine. This effect depended on the activation of N-methyl-D-aspartate (NMDA) receptors and the influx of calcium. In neurons from mice lacking gelsolin, a calcium-dependent actin-binding protein, activity-dependent stabilization of actin was impaired. Our studies provide new information on the kinetics of actin turnover in spines, its regulation by neural activity and the mechanisms involved in this regulation.
Star
Erin N
EN
Department of Molecular & Cellular Biology, Harvard University, 16 Divinity Ave., Cambridge, Massachusetts 02138, USA.
Kwiatkowski
David J
DJ
Murthy
Venkatesh N
VN
D000199:Actins / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D003712:Dendrites / Q000378:metabolism*; D047630:Depsipeptides; D018260:Gelsolin / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007202:Indicators and Reagents; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence / Q000379:methods; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*
D000199:Actins; D047630:Depsipeptides; D018260:Gelsolin; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D010456:Peptides, Cyclic; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins; C057531:jasplakinolide; D049452:Green Fluorescent Proteins; D015638:Cytochalasin D; D002118:Calcium