Furuyashiki T, Fujisawa K, Fujita A, Madaule P, Uchino S, Mishina M, Bito H, Narumiya S
Department of Pharmacology, Kyoto University Faculty of Medicine, Sakyo-ku, Kyoto 606-8315, Japan.
J Neurosci. 1999 Jan 1;19(1):109-18. doi: 10.1523/JNEUROSCI.19-01-00109.1999.
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.
膜相关鸟苷酸激酶家族的蛋白质在许多中枢突触的突触后致密区（PSD）中神经递质受体的锚定和聚集过程中发挥着重要作用。然而，对于这些多功能支架蛋白如何为突触后信号传导机制的活性和细胞类型依赖性特化提供一个特殊位点，我们所知相对较少。经典的Rho信号通路与神经发育过程中的轴突生长、树突形成和细胞迁移机制有关，但其在成熟中枢神经系统突触中的作用仍不清楚。在这里，我们提供证据表明，大脑中的一种Rho效应蛋白Citron在PSD组分中富集，并且在体内和体外均与PSD-95/突触相关蛋白（SAP）-90相互作用。Citron与PSD-95的共定位并非仅发生在有限数量神经元（如丘脑兴奋性神经元）的谷氨酸能突触中，而是肯定会发生；然而，在成年小鼠大脑的海马体和小脑中的主要神经元中未检测到Citron的表达。在一个异源系统中，Citron不仅被证明能与PSD-95形成异源复合物，还能与NMDA受体形成异源复合物。因此，Citron-PSD-95/SAP-90相互作用可能在Rho信号级联与突触NMDA受体复合物之间提供一个区域和细胞类型特异性的联系。
