Read the Editorial Highlight for this article on doi: 10.1111/jnc.12488
Spikar, a novel drebrin-binding protein, regulates the formation and stabilization of dendritic spines
Article first published online: 13 NOV 2013
© 2013 International Society for Neurochemistry
Journal of Neurochemistry
Volume 128, Issue 4, pages 507–522, February 2014
How to Cite
J. Neurochem. (2014) 128, 507–522.
- Issue published online: 9 FEB 2014
- Article first published online: 13 NOV 2013
- Accepted manuscript online: 13 OCT 2013 09:04PM EST
- Manuscript Accepted: 10 OCT 2013
- Manuscript Revised: 9 OCT 2013
- Manuscript Received: 25 JUL 2013
- T7 work was supported by Grants-in-Aid for Young Scientists. Grant Numbers: 15700285, 18700306, 21700340
- Grant-in-Aid for Scientific Research. Grant Number: 19200029
- Japan Society for the Promotion of Science (JSPS)
- dendritic spine;
- drebrin-binding protein;
- spine formation;
- transcriptional co-activator
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.
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.