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Control of inhibitory synaptic transmission by the splicing regulator Rbfox1

剪接调节因子 Rbfox1 对抑制性突触传递的控制

基本信息

批准号：
8983223
负责人：
Celine K. Vuong
金额：
$ 3.62万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8983223
关键词：
Affect Alleles Biochemical Brain Cell Fractionation Cell Nucleus Chemicals Complex Cytoplasm Disease Electrophysiology (science)Epilepsy Equilibrium Exhibits Foundations Goals High-Throughput RNA Sequencing Human Immunoprecipitation Investigation Knock-out Knockout Mice Knowledge Link Messenger RNA Molecular Mus Mutation Neurons Nuclear Pattern Physiology Play Post-Transcriptional Regulation Process Protein Family Proteins RNA RNA Interference RNA Splicing RNA-Binding Proteins Regulation Regulatory Pathway Research Proposals Role SNAP receptor Signal Transduction Synapses Synaptic Transmission Synaptic Vesicles Testing Therapeutic Transcript Work autism spectrum disorder base cell type crosslink genome-wide infancy inhibitor/antagonist inhibitory neuron insight mRNA Precursor member nervous system disorder neurodevelopment neuronal excitability paralogous gene protein expression protein function public health relevance research study synaptic function synaptogenesis vesicle-associated membrane protein vesicular release

项目摘要

DESCRIPTION (provided by applicant): Post-transcriptional regulation by RNA-binding proteins (RBPs) underlies many processes critical for proper neuronal function. Dysregulation of the brain-enriched RBP Rbfox1 has been linked to serious neurological diseases such as epilepsy and autism spectrum disorders. While Rbfox1 regulation of synaptic function is thought to contribute to these diseases, efforts to understand how RNA-level changes affect neuronal physiology remain in their infancy, and the mechanism of Rbfox1 regulation is not yet well understood. The long-term goal of understanding complex neurological diseases will require careful investigation of Rbfox1 regulation of synaptic function at the cellular and molecular level We have identified an Rbfox1 target, Vamp1, which may be involved in inhibitory synaptic transmission. We hypothesize that Rbfox1 controls neuronal excitability by regulating Vamp1 at the post-transcriptional level in a cell-type specific manner. We will combine electrophysiological and biochemical approaches in mouse neurons to 1) Determine the function of Vamp1 in the Rbfox1 knockout and 2) Define the mechanism by which Rbfox1 regulates Vamp1 transcript levels. These studies will provide mechanistic insight into Rbfox1 function and cell- type specific post-transcriptional regulation and lay the foundation for understanding the molecular basis of serious neurological diseases.