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

Authors

  • Yannan Ouyang,

    1. Department of Neurology 8111, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110, USA
    2. Department of Neurosciences 0608, UCSD, La Jolla, CA 92093, USA
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    • *

      Present addresses: Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027, USA (Y.O.); Institute of Cell Biology and Neuroscience ‘Prof E. De Robertis’, Department of Histology and Cell Biology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina 1121 (F.C.); Korea Research Institute of Bioscience and Biotechnology, Daejon 305-333, South Korea (C.-S.L.); Department of Neurology, Georg-August-University Göttingen, 37075 Göttingen, Germany (C.N.); Department of Neurology, Northwestern University Medical School,  Chicago, IL 60611, USA (J.Y.W.).

  • Michael Wong,

    1. Department of Neurology 8111, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110, USA
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  • Francisco Capani,

    1. Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
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    • *

      Present addresses: Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027, USA (Y.O.); Institute of Cell Biology and Neuroscience ‘Prof E. De Robertis’, Department of Histology and Cell Biology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina 1121 (F.C.); Korea Research Institute of Bioscience and Biotechnology, Daejon 305-333, South Korea (C.-S.L.); Department of Neurology, Georg-August-University Göttingen, 37075 Göttingen, Germany (C.N.); Department of Neurology, Northwestern University Medical School,  Chicago, IL 60611, USA (J.Y.W.).

  • Nick Rensing,

    1. Department of Neurology 8111, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110, USA
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  • Chul-Sang Lee,

    1. Department of Neurology 8111, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110, USA
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    • *

      Present addresses: Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027, USA (Y.O.); Institute of Cell Biology and Neuroscience ‘Prof E. De Robertis’, Department of Histology and Cell Biology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina 1121 (F.C.); Korea Research Institute of Bioscience and Biotechnology, Daejon 305-333, South Korea (C.-S.L.); Department of Neurology, Georg-August-University Göttingen, 37075 Göttingen, Germany (C.N.); Department of Neurology, Northwestern University Medical School,  Chicago, IL 60611, USA (J.Y.W.).

  • Qun Liu,

    1. Department of Neurology 8111, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110, USA
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  • Clemens Neusch,

    1. Department of Neurosciences 0608, UCSD, La Jolla, CA 92093, USA
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    • *

      Present addresses: Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027, USA (Y.O.); Institute of Cell Biology and Neuroscience ‘Prof E. De Robertis’, Department of Histology and Cell Biology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina 1121 (F.C.); Korea Research Institute of Bioscience and Biotechnology, Daejon 305-333, South Korea (C.-S.L.); Department of Neurology, Georg-August-University Göttingen, 37075 Göttingen, Germany (C.N.); Department of Neurology, Northwestern University Medical School,  Chicago, IL 60611, USA (J.Y.W.).

  • Maryann E. Martone,

    1. Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
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  • Jane Y. Wu,

    1. Departments of Pediatrics, Cell and Developmental Biology and Pharmacology, John F. Kennedy Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
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    • *

      Present addresses: Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027, USA (Y.O.); Institute of Cell Biology and Neuroscience ‘Prof E. De Robertis’, Department of Histology and Cell Biology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina 1121 (F.C.); Korea Research Institute of Bioscience and Biotechnology, Daejon 305-333, South Korea (C.-S.L.); Department of Neurology, Georg-August-University Göttingen, 37075 Göttingen, Germany (C.N.); Department of Neurology, Northwestern University Medical School,  Chicago, IL 60611, USA (J.Y.W.).

  • Kelvin Yamada,

    1. Department of Neurology 8111, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110, USA
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  • Mark H. Ellisman,

    1. Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
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  • Dennis W. Choi

    1. Department of Neurology 8111, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110, USA
    2. Merck Research Laboratories, West Point, PA 19486, USA
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Dr Y. Ouyang, as above.1
E-mail: ouyangy@neuro.wustl.edu

Abstract

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.

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