RT Journal Article
SR Electronic
T1 FXR2P Exerts a Positive Translational Control and Is Required for the Activity-Dependent Increase of PSD95 Expression
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9402
OP 9408
DO 10.1523/JNEUROSCI.4800-14.2015
VO 35
IS 25
A1 Fernández, Esperanza
A1 Li, Ka Wan
A1 Rajan, Nicholas
A1 De Rubeis, Silvia
A1 Fiers, Mark
A1 Smit, August B.
A1 Achsel, Tilmann
A1 Bagni, Claudia
YR 2015
UL http://www.jneurosci.org/content/35/25/9402.abstract
AB In brain, specific RNA-binding proteins (RBPs) associate with localized mRNAs and function as regulators of protein synthesis at synapses exerting an indirect control on neuronal activity. Thus, the Fragile X Mental Retardation protein (FMRP) regulates expression of the scaffolding postsynaptic density protein PSD95, but the mode of control appears to be different from other FMRP target mRNAs. Here, we show that the fragile X mental retardation-related protein 2 (FXR2P) cooperates with FMRP in binding to the 3′-UTR of mouse PSD95/Dlg4 mRNA. Absence of FXR2P leads to decreased translation of PSD95/Dlg4 mRNA in the hippocampus, implying a role for FXR2P as translation activator. Remarkably, mGluR-dependent increase of PSD95 synthesis is abolished in neurons lacking Fxr2. Together, these findings show a coordinated regulation of PSD95/Dlg4 mRNA by FMRP and FXR2P that ultimately affects its fine-tuning during synaptic activity.