Synaptic clustering of AMPA receptors by the extracellular immediate-earlygene product Narp

Narp (neuronal activity-regulated pentraxin) is a secreted immediate-early gene (IEG) regulated by synaptic activity in brain. In this study, we demon strate that Narp possesses several properties that make it likely to play a key role in excitatory synaptogenesis. Narp is shown to be selectively enr iched at excitatory synapses on neurons from both the hippocampus and spina l cord. Overexpression of recombinant Narp increases the number of excitato ry but not inhibitory synapses in cultured spinal neurons. In transfected H EK 293T cells, Narp interacts with itself, forming large surface clusters t hat 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 fac tor for AMPA receptors.