Article abstract
Nature Neuroscience 10, 427 - 435 (2007)
Published online: 4 March 2007 | doi:10.1038/nn1867
Activity-dependent AIDA-1 nuclear signaling regulates nucleolar numbers and protein synthesis in neurons
Bryen A Jordan1, Brian D Fernholz2, Latika Khatri1 & Edward B Ziff1,2
Abstract
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.
- Department of Biochemistry, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.
- Program in Neuroscience and Physiology, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Correspondence to: Bryen A Jordan1 e-mail: jordab01@med.nyu.edu
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