Retinoic acid regulates RARalpha-mediated control of translation in dendritic RNA granules during homeostatic synaptic plasticity.
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 RARalpha, a member of the nuclear RA receptor family. This result raised the question of where RARalpha 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 RARalpha in the dendritic RNA granules and activates local GluR1 synthesis in these RNA granules. Importantly, the same RNA granules that contain RARalpha also exhibit an accumulation of GluR1 protein but with a much slower time course than that of RARalpha, suggesting that the former regulates the latter. Taken together, our results provide a direct link between dendritically localized RARalpha and local GluR1 synthesis in RNA granules during RA-mediated synaptic signaling in homeostatic synaptic plasticity.
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3200, USA.
Bita
B
Maghsoodi
Michael M
MM
Poon
Christine I
CI
Nam
Jason
J
Aoto
Pamela
P
Ting
Lu
L
Chen
D000818:Animals; D003594:Cytoplasmic Granules / Q000737:chemistry; D003712:Dendrites / Q000235:genetics* / Q000648:ultrastructure; D051379:Mice; D009473:Neuronal Plasticity; D014176:Protein Biosynthesis; D018091:Receptors, AMPA / Q000096:biosynthesis*; D018168:Receptors, Retinoic Acid / Q000502:physiology*; D000072482:Retinoic Acid Receptor alpha; D009435:Synaptic Transmission; D014212:Tretinoin / Q000494:pharmacology*
D018091:Receptors, AMPA; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin; C000607072:Rara protein, mouse