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The Journal of Neuroscience, June 1, 2002, 22(11):4487-4498

Synaptically Targeted Narp Plays an Essential Role in the Aggregation of AMPA Receptors at Excitatory Synapses in Cultured Spinal Neurons

Richard O'Brien^{1, 2, *}, Desheng Xu^{2, *}, Ruifa Mi¹, Xiaopei Tang¹, Carsten Hopf², and Paul Worley^{1, 2}

Departments of ¹ Neurology and ² Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287

Neuronal activity regulated pentraxin (Narp) has been implicated in the aggregation of AMPA-type glutamate receptors (GluR) at excitatory synapses. In the present paper, we examine the role of endogenous Narp in excitatory synapse formation by using novel, dominant-negative Narp mutants (dnNarp) that selectively bind endogenous Narp and prevent its accumulation at synapses. Axons from neurons transfected with wild-type Narp showed an increase in their ability to cluster AMPA receptors on spinal neurons, whereas axons from neurons transfected with dnNarp showed a marked decrease in their ability to induce GluR1 clusters on contacted dendrites. Despite their marked effect at excitatory synapses, dnNarp and wild-type Narp had no effect on the postsynaptic clustering of the inhibitory protein gephyrin or the percentage of contacts associated with staining for the presynaptic vesicle proteins GAD or synaptophysin. Use of the dnNarp mutants to suppress endogenous Narp expression by postsynaptic dendrites showed a complementary role for dendritic Narp in the clustering of synaptic AMPA receptors, as well as a reduction in the total number of excitatory synapses on transfected neurons. Together these experiments suggest an important role for Narp in the formation of excitatory synapses in cultured spinal neurons.

Key words: Narp; spinal neurons; excitatory synapses; glutamate receptors; synaptogenesis; pentraxin

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^* R.O. and D.X. contributed equally to this work.

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22114487-12$05.00/0

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