Activity-dependent AIDA-1 nuclear signaling regulates nucleolar numbers and protein synthesis in neurons.
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.
Jordan
Bryen A
BA
Department of Biochemistry, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA. jordab01@med.nyu.edu
Fernholz
Brian D
BD
Khatri
Latika
L
Ziff
Edward B
EB
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002466:Cell Nucleolus / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure*; D010750:Phosphoproteins / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology*; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000378:metabolism; D014162:Transfection / Q000379:methods; D062826:Zonula Occludens-1 Protein
D048868:Adaptor Proteins, Signal Transducing; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C569042:TJP1 protein, human; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D049452:Green Fluorescent Proteins; D016202:N-Methylaspartate