Transient decrease in F-actin may be necessary for translocation of proteins into dendritic spines

• Published in: The European journal of neuroscience Vol. 22; no. 12; pp. 2995 - 3005
• Main Authors: Ouyang, Yannan, Wong, Michael, Capani, Francisco, Rensing, Nick, Lee, Chul-Sang, Liu, Qun, Neusch, Clemens, Martone, Maryann E., Wu, Jane Y., Yamada, Kelvin, Ellisman, Mark H., Choi, Dennis W.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.12.2005
• Subjects: 2-Amino-5-phosphonovalerate - pharmacology; Actin Depolymerizing Factors - metabolism; Actins - metabolism; Animals; Blotting, Western - methods; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Cells, Cultured; dendritic spine; Dendritic Spines - metabolism; Dendritic Spines - ultrastructure; Depsipeptides - pharmacology; Dextrans - metabolism; Disks Large Homolog 4 Protein; Dose-Response Relationship, Radiation; Electric Stimulation - methods; Embryo, Mammalian; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Excitatory Postsynaptic Potentials - radiation effects; F-actin; Fluorescent Antibody Technique - methods; Green Fluorescent Proteins - metabolism; Hippocampus - cytology; In Vitro Techniques; information storage; Intracellular Signaling Peptides and Proteins - metabolism; Long-Term Potentiation - drug effects; Long-Term Potentiation - physiology; Long-Term Potentiation - radiation effects; LTP; Membrane Proteins - metabolism; Microscopy, Immunoelectron - methods; Microtubule-Associated Proteins - metabolism; Neurons - cytology; Neurons - drug effects; Neurons - physiology; Patch-Clamp Techniques - methods; Phosphorylation - drug effects; Phosphorylation - radiation effects; Potassium Chloride - pharmacology; protein translocation; Protein Transport - drug effects; Protein Transport - physiology; Rats; synaptic specificity; Time Factors; Transfection
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.1460-9568.2005.04521.x

It remains poorly understood as to how newly synthesized proteins that are required to act at specific synapses are translocated into only selected subsets of potentiated dendritic spines. Here, we report that F‐actin, a major component of the skeletal structure of dendritic spines, may contribute to the regulation of synaptic specificity of protein translocation. We found that the stabilization of F‐actin blocked the translocation of GFP‐CaMKII and inhibited the diffusion of 3‐kDa dextran into spines (in 2–3 weeks cultures). Neuronal activation in hippocampal slices and cultured neurons led to an increase in the activation (decrease in the phosphorylation) of the actin depolymerization factor, cofilin, and a decrease in F‐actin. Furthermore, the induction of long‐term potentiation by tetanic stimulation induced local transient depolymerization of F‐actin both in vivo and in hippocampal slices (8–10 weeks), and this local F‐actin depolymerization was blocked by APV, a N‐methyl‐d‐aspartate (NMDA) receptor antagonist. These results suggest that F‐actin may play a role in synaptic specificity by allowing protein translocation into only potentiated spines, gated through its depolymerization, which is probably triggered by the activation of NMDA receptors.