Synaptic clustering of AMPA receptors by the extracellular immediate-early gene product Narp.
Narp (neuronal activity-regulated pentraxin) is a secreted immediate-early gene (IEG) regulated by synaptic activity in brain. In this study, we demonstrate that Narp possesses several properties that make it likely to play a key role in excitatory synaptogenesis. Narp is shown to be selectively enriched at excitatory synapses on neurons from both the hippocampus and spinal cord. Overexpression of recombinant Narp increases the number of excitatory but not inhibitory synapses in cultured spinal neurons. In transfected HEK 293T cells, Narp interacts with itself, forming large surface clusters that coaggregate AMPA receptor subunits. Moreover, Narp-expressing HEK 293T cells can induce the aggregation of neuronal AMPA receptors. These studies support a model in which Narp functions as an extracellular aggregating factor for AMPA receptors.
O'Brien
R J
RJ
Howard Hughes Medical Institute, and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Xu
D
D
Petralia
R S
RS
Steward
O
O
Huganir
R L
RL
Worley
P
P
D000818:Animals; D001369:Axons / Q000378:metabolism; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000096:biosynthesis / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism / Q000502:physiology; D006624:Hippocampus / Q000166:cytology; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000502:physiology*; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology; D013569:Synapses / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D000099153:Pentraxins
D002097:C-Reactive Protein; D017874:Immediate-Early Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D000099153:Pentraxins; C104723:glutamate receptor ionotropic, AMPA 3