Citron, a Rho-target, interacts with PSD-95/SAP-90 at glutamatergic synapses in the thalamus

Proteins of the membrane-associated guanylate kinase family play an importa nt role in the anchoring and clustering of neurotransmitter receptors in th e postsynaptic density (PSD) at many central synapses. However, relatively little is known about how these multifunctional scaffold proteins might pro vide a privileged site for activity- and cell type-dependent specification of the postsynaptic signaling machinery. Rho signaling pathway has classica lly been implicated in mechanisms of axonal outgrowth, dendrogenesis, and c ell migration during neural development, but its contribution remains uncle ar at the synapses in the mature CNS. Here, we present evidence that Citron , a Rho-effector in the brain, is enriched in the PSD fraction and interact s with PSD-95/synapse-associated protein (SAP)-90 both in vivo and in vitro . Citron colocalization with PSD-95 occurred, not exclusively but certainly , at glutamatergic synapses in a limited set of neurons, such as the thalam ic excitatory neurons; Citron expression, however, could not be detected in the principal neurons of the hippocampus and the cerebellum in the adult m ouse brain. In a heterologous system, Citron was shown to form a heteromeri c complex not only with PSD-95 but also with NMDA receptors. Thus, Citron-P SD-95/SAP-90 interaction may provide a region- and cell type-specific link between the Rho signaling cascade and the synaptic NMDA receptor complex.