Retinoic acid regulates RARα-mediated control of translation in dendritic RNA granules during homeostatic synaptic plasticity

doi:10.1073/pnas.0804801105

Retinoic acid regulates RARα-mediated control of translation in dendritic RNA granules during homeostatic synaptic plasticity

*Department of Molecular and Cell Biology and
^†Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720-3200

Edited by Thomas C. Südhof, Stanford University School of Medicine, Palo Alto, CA, and approved August 27, 2008 (received for review May 16, 2008)

Abstract

Homeostatic plasticity is thought to play an important role in maintaining the stability of neuronal circuits. During one form of homeostatic plasticity, referred to as synaptic scaling, activity blockade leads to a compensatory increase in synaptic transmission by stimulating in dendrites the local translation and synaptic insertion of the AMPA receptor subunit GluR1. We have previously shown that all-trans retinoic acid (RA) mediates activity blockade-induced synaptic scaling by activating dendritic GluR1 synthesis and that this process requires RARα, a member of the nuclear RA receptor family. This result raised the question of where RARα is localized in dendrites and whether its localization is regulated by RA and/or activity blockade. Here, we show that activity blockade or RA treatment in neurons enhances the concentration of RARα in the dendritic RNA granules and activates local GluR1 synthesis in these RNA granules. Importantly, the same RNA granules that contain RARα also exhibit an accumulation of GluR1 protein but with a much slower time course than that of RARα, suggesting that the former regulates the latter. Taken together, our results provide a direct link between dendritically localized RARα and local GluR1 synthesis in RNA granules during RA-mediated synaptic signaling in homeostatic synaptic plasticity.

Footnotes

^‡To whom correspondence should be addressed. E-mail: luchen{at}berkeley.edu
Author contributions: M.M.P., J.A., and L.C. designed research; B.M., M.M.P., C.I.N., J.A., P.T., and L.C. performed research; J.A. contributed new reagents/analytic tools; B.M., M.M.P., C.I.N., J.A., and L.C. analyzed data; and L.C. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0804801105/DCSupplemental.