Spikar, a novel drebrin‐binding protein, regulates the formation and stabilization of dendritic spines

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  • Kenichi Kato
    Department of Neurobiology and Behavior Gunma University Graduate School of Medicine Maebashi Japan
  • Hiroyuki Yamazaki
    Department of Neurobiology and Behavior Gunma University Graduate School of Medicine Maebashi Japan
  • Nobuhiko Kojima
    Department of Neurobiology and Behavior Gunma University Graduate School of Medicine Maebashi Japan
  • Eiji Hirose
    National Center for Geriatrics and Gerontology Obu Japan
  • Toshiyuki Mizui
    Department of Neurobiology and Behavior Gunma University Graduate School of Medicine Maebashi Japan
  • Toshiharu Iwasaki
    Integrative Physiology Gunma University Graduate School of Medicine Maebashi Japan
  • Kenji Hanamura
    Department of Neurobiology and Behavior Gunma University Graduate School of Medicine Maebashi Japan
  • Hideto Takahashi
    Department of Neurobiology and Behavior Gunma University Graduate School of Medicine Maebashi Japan
  • Reiko T. Roppongi
    Department of Neurobiology and Behavior Gunma University Graduate School of Medicine Maebashi Japan
  • Yuko Sekino
    Department of Neurobiology and Behavior Gunma University Graduate School of Medicine Maebashi Japan
  • Nozomu Mori
    National Center for Geriatrics and Gerontology Obu Japan
  • Tomoaki Shirao
    Department of Neurobiology and Behavior Gunma University Graduate School of Medicine Maebashi Japan
  • Noriyuki Koibuchi
    Integrative Physiology Gunma University Graduate School of Medicine Maebashi Japan

Bibliographic Information

Published
2013-11-13
Resource Type
journal article
Rights Information
  • http://onlinelibrary.wiley.com/termsAndConditions#vor
DOI
  • 10.1111/jnc.12486
Publisher
Wiley

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<jats:title>Abstract</jats:title><jats:p>Dendritic spines are small, actin‐rich protrusions on dendrites, the development of which is fundamental for the formation of neural circuits. The actin cytoskeleton is central to dendritic spine morphogenesis. Drebrin is an actin‐binding protein that is thought to initiate spine formation through a unique drebrin‐actin complex at postsynaptic sites. However drebrin overexpression in neurons does not increase the final density of dendritic spines. In this study, we have identified and characterized a novel drebrin‐binding protein, spikar. Spikar is localized in cell nuclei and dendritic spines, and accumulation of spikar in dendritic spines directly correlates with spine density. A reporter gene assay demonstrated that spikar acts as a transcriptional co‐activator for nuclear receptors. We found that dendritic spine, but not nuclear, localization of spikar requires drebrin.<jats:styled-content style="fixed-case">RNA</jats:styled-content>‐interference knockdown and overexpression experiments demonstrated that extranuclear spikar regulates dendritic spine density by modulating<jats:italic>de novo</jats:italic>spine formation and retraction of existing spines. Unlike drebrin, spikar does not affect either the morphology or function of dendritic spines. These findings indicate that drebrin‐mediated postsynaptic accumulation of spikar regulates spine density, but is not involved in regulation of spine morphology.<jats:boxed-text content-type="graphic" position="anchor"><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" mimetype="image/png" position="anchor" specific-use="enlarged-web-image" xlink:href="graphic/jnc12486-fig-0008-m.png"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text></jats:p><jats:p>This study identified a novel drebrin‐binding protein, spikar, which is a novel transcriptional co‐activator. Drebrin serves to anchor spikar in dendritic spines.　Spikar knockdown decreases a spine density by attenuating the spine stability and inhibiting de novo spine formation. Extranuclear spikar rescues the spine decrease in spikar knockdowned neurons. Spikar overexpression increases a spine density in drebrin‐dependent manner.</jats:p>

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