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1: Nat Neurosci. 2007 Apr;10(4):427-35. Epub 2007 Mar 4.
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Activity-dependent AIDA-1 nuclear signaling regulates nucleolar numbers and protein synthesis in neurons.

Jordan BA, Fernholz BD, Khatri L, Ziff EB.

Department of Biochemistry, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA. jordab01@med.nyu.edu

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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PMID: 17334360 [PubMed - indexed for MEDLINE]