title: Citron, a Rho-target, interacts with PSD-95/SAP-90 at glutamatergic synapses in the thalamus.
abstract: Proteins of the membrane-associated guanylate kinase family play an important role in the anchoring and clustering of neurotransmitter receptors in the postsynaptic density (PSD) at many central synapses. However, relatively little is known about how these multifunctional scaffold proteins might provide a privileged site for activity- and cell type-dependent specification of the postsynaptic signaling machinery. Rho signaling pathway has classically been implicated in mechanisms of axonal outgrowth, dendrogenesis, and cell migration during neural development, but its contribution remains unclear 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 interacts 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 thalamic excitatory neurons; Citron expression, however, could not be detected in the principal neurons of the hippocampus and the cerebellum in the adult mouse brain. In a heterologous system, Citron was shown to form a heteromeric complex not only with PSD-95 but also with NMDA receptors. Thus, Citron-PSD-95/SAP-90 interaction may provide a region- and cell type-specific link between the Rho signaling cascade and the synaptic NMDA receptor complex.
authors.affiliation: Department of Pharmacology, Kyoto University Faculty of Medicine, Sakyo-ku, Kyoto 606-8315, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Furuyashiki
authors.forename: K
authors.initials: K
authors.lastname: Fujisawa
authors.forename: A
authors.initials: A
authors.lastname: Fujita
authors.forename: P
authors.initials: P
authors.lastname: Madaule
authors.forename: S
authors.initials: S
authors.lastname: Uchino
authors.forename: M
authors.initials: M
authors.lastname: Mishina
authors.forename: H
authors.initials: H
authors.lastname: Bito
authors.forename: S
authors.initials: S
authors.lastname: Narumiya
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D006224:Cricetinae; D000076122:Disks Large Homolog 4 Protein; D018698:Glutamic Acid / Q000502:physiology; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012234:Rho Factor / Q000378:metabolism*; D000074407:SAP90-PSD95 Associated Proteins; D015398:Signal Transduction / Q000502:physiology*; D013788:Thalamus / Q000378:metabolism / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D012234:Rho Factor; D000074407:SAP90-PSD95 Associated Proteins; C033652:postsynaptic density proteins; D018698:Glutamic Acid; C115635:citron-kinase; D017346:Protein Serine-Threonine Kinases; D051528:Guanylate Kinases