Role of Leucine-rich Acidic Proteins in Neuronal Development

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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.