TECH: A NOVEL RHO GEF FAMILY MEMBER EXPRESSED IN NEURONS

由于神经元可塑性的异常与各种神经和精神疾病有关，神经科学研究的首要任务之一是破译调节这一过程的分子机制。最近的研究集中在神经元形态的动态变化，似乎在神经元可塑性中发挥不可或缺的作用。虽然对介导和调节神经元形态变化的信号通路知之甚少，但最近的研究表明，Rho家族的GTP酶在这一过程中起着重要作用。因此，旨在阐明这些关键信号分子在神经元中的调节和功能的研究是必要的。R 03申请寻求资金进行探索性研究，旨在获得Tech功能的线索，Tech是我们实验室分离的一种新的大脑cDNA。初步研究表明，Tech转录本在皮质和海马中富集，并在神经元中表达。Tech cDNA序列的分析表明，它是调节Rho GTP酶活性的Rho GEF蛋白家族的成员。因此，阐明Tech的功能可能为神经元中Rho信号通路的调节和功能提供新的见解，这是一个重要的研究领域。为了探索Tech的功能，我们计划：1）确定Tech转录本是否编码由其cDNA序列预测的功能性Rho GEF，2）确定Tech蛋白在神经元内的定位，以及3）进行旨在鉴定与其推定的C-末端PDZ配体基序结合的伴侣蛋白的实验的初始阶段。

As abnormalities in neuronal plasticity have been implicated in a wide variety of neurological and psychiatric disorders, one of the top priorities of neuroscience research is to decipher the molecular mechanisms that regulate this process. Recent studies have focused attention on the dynamic changes in neuronal morphology that appear to play an integral role in neuronal plasticity. Although the signaling pathways that mediate and regulate changes in neuronal morphology are poorly understood, recent studies indicate that the Rho family of GTPases play an important in this process. Accordingly, studies aimed at elucidating the regulation and function of these key signaling molecules in neurons are warranted. This R03 application seeks funds to conduct exploratory studies aimed at gaining clues to the function of Tech, a novel brain cDNA isolated by our laboratory. Preliminary studies indicate that the Tech transcript is enriched in cortex and hippocampus and is expressed in neurons. Analysis of the Tech cDNA sequence indicates that it is a member of the Rho GEF family of proteins that regulate the activity of Rho GTPases. Thus, elucidating the function of Tech is likely to provide new insights into the regulation and function of Rho signaling pathways in neurons, an important area of investigation. To explore the function of Tech, we plan to: 1) determine whether the Tech transcript encodes a functional Rho GEF as predicted by its cDNA sequence, 2) define the localization of Tech protein within neurons, and 3) carry out the initial phases of experiments aimed at identifying partner proteins that bind to its putative C-terminal PDZ ligand motif.