The role of local mRNA translation in the regulation of dendritic spine morphogenesis

局部 mRNA 翻译在树突棘形态发生调节中的作用

• 批准号: 51504094
• 负责人: Professor Dr. Carlos Bas Orth
• 金额: --
• 依托单位: Anatomie I - Klinische Neuroanatomie
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/51504094?language=en
• 关键词: role; local; mRNA; translation; regulation

Mental retardation and autism are a highly prevalent and diverse group of disorders for which there is no effective treatment. A common feature of these diseases is that nerve cells from affected patients exhibit abnormally-shaped dendritic spines, structures that serve to form synapses. A critical question in neurodevelopmental disease research is: what causes the abnormal spine morphology in these diseases? Recently, the synthesis of proteins at specific target sites within a cell (“local translation”) has emerged as a novel mechanism for gene regulation that is involved in the control of cell shape and function. In Fragile X syndrome (FXS), the most common form of inherited mental retardation, this mechanism is impaired. Thus, the present project focuses on two questions to explore the role of local translation in the regulation of spine shape: (1) Is the shape of dendritic spines controled by the local translation of a specific regulatory potein (RhoA)? (2) Is this specific regulation impaired in FXS and, thereby, leads to abnormally-shaped spines? In summary, this project might elucidate a novel mechanism for the control of dendritic spine shape and may provide a link between the genetic deficit and the neuroanatomical abnormalities in FXS. Because the regulation of dendritic spine shape has implications for many mental diseases as well as for physiological processes like learning and memory, this project might have a general impact on our understanding of brain function.

精神发育迟滞和自闭症是一种非常普遍和多样化的疾病，没有有效的治疗方法。这些疾病的一个共同特征是，来自受影响患者的神经细胞显示出异常形状的树突棘，这是一种用于形成突触的结构。神经发育疾病研究中的一个关键问题是：这些疾病中脊柱形态异常的原因是什么？最近，蛋白质在细胞内特定靶点的合成(“局部翻译”)已经成为一种新的基因调控机制，它涉及到细胞形状和功能的控制。脆性X综合征(FXS)是遗传性智力低下的最常见形式，这种机制受到损害。因此，本项目集中于两个问题来探讨局部翻译在脊柱形状调节中的作用：(1)树突棘的形状是否受特定调控蛋白(RhoA)的局部翻译控制？(2)这种特定调控在FXS中是否受损，从而导致脊柱形状异常？综上所述，该项目可能阐明一种控制树突棘形状的新机制，并可能在FXS的遗传缺陷和神经解剖异常之间提供联系。由于树突棘形状的调节与许多精神疾病以及学习和记忆等生理过程有关，这个项目可能会对我们对大脑功能的理解产生普遍影响。