Neuronal development, plasticity and survival require activity-dependent synapse-to-nucleus signaling. Most studies implicate an activity-dependent regulation of gene expression in this phenomenon. However, little is known about other nuclear functions that are regulated by synaptic activity. Here we show that a newly identified component of rat postsynaptic densities (PSDs), AIDA-1d, can regulate global protein synthesis by altering nucleolar numbers. AIDA-1d binds to the first two postsynaptic density–95/Discs large/zona occludens-1 (PDZ) domains of the scaffolding protein PSD-95 via its C-terminal three amino acids. Stimulation of NMDA receptors (NMDARs), which are also bound to PSD-95, results in a Ca2+-independent translocation of AIDA-1d to the nucleus, where it couples to Cajal bodies and induces Cajal body–nucleolar association. Long-term neuronal stimulation results in an AIDA-1–dependent increase in nucleolar numbers and protein synthesis. We propose that AIDA-1d mediates a link between synaptic activity and control of protein biosynthetic capacity by regulating nucleolar assembly.
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We thank A. Lamond (Univ of Dundee) and E. Tan (Scripps Institute) for antibodies to p80-coilin and S. De Souza for PSD-95 plasmid. This work was supported by grants from the US National Institutes of Health (to E.B.Z., R01 MH67229, and B.A.J., K01 MH073759-02).
The authors declare no competing financial interests.
Alignment of AIDA-1 isoform sequences. (PDF 1274 kb)
Primary hippocampal neurons grown on 6-cm plates containing coverslip bottoms and expressing eGFP–AIDA-1d were placed into an environmental chamber (37 °C and 5% CO2, Carl Zeiss) for 2 h to equilibrate and imaged every 20 s. (MOV 1895 kb)
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