Role of Leucine-rich Acidic Proteins in Neuronal Development

富含亮氨酸的酸性蛋白在神经元发育中的作用

• 批准号: 7789230
• 负责人: Puneet Opal
• 金额: $ 7.63万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7789230
• 关键词: Address; Architecture; Binding; Brain; Caregivers; Cell Line; Cell Nucleus; Cells; Cerebellum; Child; Chromatin; Cytoplasm; Cytoskeletal Gene; Cytoskeleton; Data; Defect; Development; Developmental Process; Disease; Epigenetic Process; Equilibrium; Family; Gene Expression; Gene Silencing; Genes; Genetic Transcription; Grant; Histone Acetylation; Histones; Individual; Knockout Mice; Laboratories; Leucine; Life; Light; Location; Masks; Microtubule-Associated Proteins; Microtubules; Molecular; Mus; N-terminal; Neurites; Neuronal Differentiation; Neurons; Nuclear Protein; Nuclear Proteins; Patients; Pattern; Play; Positioning Attribute; Process; Property; Protein Binding; Proteins; Quality of life; Repression; Research Personnel; Role; Speed; Synapses; Syndrome; Tail; Testing; Time; Transcriptional Regulation; Transferase; base; gene repression; in vivo; insight; knock-down; member; nervous system development; neurofilament; neuron development; nucleocytoplasmic transport; postnatal; promoter; trafficking

DESCRIPTION (Provided by Applicant): The ability of neurons to extend neurites is critical for synaptic formation and neuronal function. However, the molecular basis of neurite extension is largely unknown. To understand this fundamental process, the investigators have focused on the leucine-rich acidic nuclear protein (LANP), a protein that is expressed at particularly high levels in developing neurons from the early postnatal brain, in particular the cerebellum, at a time and location when neurons extend to processes to form functional networks. LANP is a nucleocytoplasmic shuttling protein. In the cytoplasm, LANP binds to all classes of structural microtubule-associated-proteins (MAPs); while in the nucleus LANP regulates transcription by inhibiting histone acetyl transferases (HATs). The investigators' preliminary data inspire the intriguing hypothesis that LANP plays a role in development by a dual role: (a) regulating the expression of genes critical for neurite outgrowth, and (b) modulating the properties of the neuronal cytoskeleton. This application makes use of the LANP null mice that the investigators have generated to address the role of LANP in neurite outgrowth. Defects in neurite outgrowth underlie a number of neurodevelopmental syndromes that negatively impact the life of young children and their care-givers. This application will help us to gain insights into the molecular basis of these disorders. RELEVANCE: Defects in proteins that regulate gene expression underlie a number of neurodevelopmental syndromes that negatively impact the quality of life of young patients and their care-givers. The investigators' laboratory is focusing on elucidating the properties of a protein called LANP that appear to play an important role as a regulator of neurite outgrowth.

描述（由申请人提供）：神经元延伸神经突的能力对于突触形成和神经元功能至关重要。 然而，神经突延伸的分子基础在很大程度上是未知的。 为了理解这一基本过程，研究人员将重点放在富含亮氨酸的酸性核蛋白（LANP）上，这是一种在出生后早期大脑（特别是小脑）发育中的神经元中以特别高的水平表达的蛋白质，在神经元延伸到形成功能网络的过程的时间和位置。 LANP是一种核质穿梭蛋白。 在细胞质中，LANP与所有类型的结构微管相关蛋白（MAP）结合;而在细胞核中，LANP通过抑制组蛋白乙酰基转移酶（HAT）来调节转录。 研究人员的初步数据激发了一个有趣的假设，即LANP通过双重作用在发育中发挥作用：（a）调节神经突生长关键基因的表达，（B）调节神经元细胞骨架的特性。 该应用利用研究人员已经产生的LANP缺失小鼠来解决LANP在神经突生长中的作用。 神经突生长缺陷是许多神经发育综合征的基础，这些综合征对幼儿及其照顾者的生活产生负面影响。 这一应用将帮助我们深入了解这些疾病的分子基础。 相关性：调节基因表达的蛋白质缺陷是许多神经发育综合征的基础，这些综合征对年轻患者及其护理人员的生活质量产生负面影响。 研究人员的实验室正致力于阐明一种名为LANP的蛋白质的特性，这种蛋白质似乎在神经突生长的调节中起着重要作用。