Yamagata K, Sanders L K, Kaufmann W E, Yee W, Barnes C A, Nathans D, Worley P F
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
J Biol Chem. 1994 Jun 10;269(23):16333-9.
Neuronal activity results in long term cellular changes that underlie normal brain development and synaptic plasticity. To examine the molecular basis of activity-dependent plasticity, we have used differential cloning techniques to identify genes that are rapidly induced in brain neurons by synaptic activity. Here we describe an inducible novel member of the Ras family of small GTP-binding proteins we have termed Rheb. rheb mRNA is rapidly and transiently induced in hippocampal granule cells by seizures and by NMDA-dependent synaptic activity in the long term potentiation paradigm. The predicted amino acid sequence of Rheb is most closely homologous to yeast Ras1 and human Rap2. The putative GTP binding regions are highly conserved. A bacterial fusion protein of Rheb binds GTP and exhibits intrinsic GTPase activity. Like Ha-Ras, the carboxylterminal sequence encodes a CAAX box that is predicted to signal post-translational farnesylation and to target Rheb to specific membranes. rheb mRNA is expressed at comparatively high levels in normal adult cortex as well as a number of peripheral tissues, including lung and intestine. In the developing brain, rheb mRNA is expressed at relatively high levels in embryonic day 19 cortical plate, and expression remains at stable levels throughout the remainder of prenatal and postnatal development. Its close homology with ras and its rapid inducibility by receptor-dependent synaptic activity suggest that rheb may play an important role in long term activity-dependent neuronal responses.
神经元活动会导致长期的细胞变化，这些变化是正常大脑发育和突触可塑性的基础。为了研究活动依赖性可塑性的分子基础，我们使用差异克隆技术来鉴定那些在脑神经元中被突触活动快速诱导的基因。在此，我们描述了一种小GTP结合蛋白Ras家族的可诱导新成员，我们将其命名为Rheb。在癫痫发作以及长期增强模式下的NMDA依赖性突触活动中，海马颗粒细胞中的rheb mRNA会被快速且短暂地诱导。Rheb的预测氨基酸序列与酵母Ras1和人类Rap2最为同源。假定的GTP结合区域高度保守。Rheb的细菌融合蛋白结合GTP并表现出内在的GTP酶活性。与Ha-Ras一样，羧基末端序列编码一个CAAX框，预计该框会发出翻译后法尼基化信号并将Rheb靶向特定膜。rheb mRNA在正常成年皮质以及包括肺和肠道在内的许多外周组织中以相对较高的水平表达。在发育中的大脑中，rheb mRNA在胚胎第19天的皮质板中以相对较高的水平表达，并且在产前和产后发育的其余阶段表达保持稳定水平。它与ras的密切同源性以及受体依赖性突触活动对其的快速诱导表明，rheb可能在长期活动依赖性神经元反应中起重要作用。
