title: Spikar, a novel drebrin-binding protein, regulates the formation and stabilization of dendritic spines.
abstract: 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. RNA-interference knockdown and overexpression experiments demonstrated that extranuclear spikar regulates dendritic spine density by modulating de novo 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.
authors.affiliation: Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Kojima
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kato
authors.forename: Eiji
authors.initials: E
authors.lastname: Hirose
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Iwasaki
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Mizui
authors.forename: Hideto
authors.initials: H
authors.lastname: Takahashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Hanamura
authors.forename: Reiko T
authors.initials: RT
authors.lastname: Roppongi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Koibuchi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sekino
authors.forename: Nozomu
authors.initials: N
authors.lastname: Mori
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Shirao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D049229:Dendritic Spines / Q000502:physiology*; D055724:Electrophysiological Phenomena; D005260:Female; D017930:Genes, Reporter / Q000235:genetics; D005822:Genetic Vectors; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D009479:Neuropeptides / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D034622:RNA Interference; D051381:Rats; D012441:Saccharomyces cerevisiae; D013347:Subcellular Fractions / Q000378:metabolism; D013569:Synapses / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology*; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D009479:Neuropeptides; D015534:Trans-Activators; C587626:Zmynd8 protein, rat; C053386:drebrins
keywords: dendritic spine; drebrin-binding protein; spine formation; transcriptional co-activator