Role of Leucine-rich Acidic Proteins in Neuronal Development

描述（由申请人提供）：神经元延伸神经突的能力对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了富含亮氨酸的酸性核蛋白（LANP）上，这种蛋白质在出生后早期大脑（尤其是小脑）发育中的神经元中表达水平特别高，而此时神经元延伸到形成功能网络的过程中。

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.