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Investigating How Chromatin Remodeling Affects Endocytosis and Synaptic Organization

研究染色质重塑如何影响内吞作用和突触组织

基本信息

批准号：
10438398
负责人：
FAITH L LIEBL
金额：
$ 42.29万
依托单位：
SOUTHERN ILLINOIS UNIV AT EDWARDSVILLE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10438398
关键词：
Adult Affect Behavior Binding CHARGE syndrome CHD7 gene Cell Adhesion Molecules Cell physiology Cells Chromatin Communication Complex Corpus striatum structure DNA Development Disease Drosophila genus Endocytosis Ensure Enzymes Epigenetic Process Event Family Gene Expression Gene Family Genes Genetic Transcription Glutamate Receptor Glutamates Goals Grant Histones Human Intellectual functioning disability Knowledge Larva Lead Link Lysine Mediating Membrane Proteins Memory Motor Neurons Multiprotein Complexes Mus Muscle Mutation Nerve Degeneration Neurodegenerative Disorders Neurodevelopmental Disorder Neurons Orthologous Gene Pathology Pharmacology Phenocopy Phenotype Physiology Polycomb Post-Translational Protein Processing Process Protein Binding Domain Protein Family Proteins Repression Research Risk Factors Role Series Signal Transduction Site Structure Students Synapses Synaptic Membranes Synaptic plasticity System Training Transcript Transcriptional Regulation Work autism spectrum disorder brain cell chromatin remodeling experience experimental study fly gene product genetic manipulation helicase histone modification insight knock-down link protein mutant neurodevelopment neuropsychiatric disorder neurotransmission novel postsynaptic presynaptic promoter protein complex synaptic function trafficking undergraduate student

项目摘要

Chromatin remodeling proteins work in complexes to regulate the accessibility of DNA thereby determining whether transcription occurs. Chromatin remodeling is important for all cellular processes but how chromatin remodeling proteins work cooperatively with or in opposition to additional proteins to influence synaptic activity is not well understood. Chromatin remodeling proteins, including the chromodomain helicase binding domain (CHD) protein family, are implicated in neurodevelopmental disorders, synaptic plasticity, and neurodegenerative diseases. The goals of the proposed work are to better understand how the CHD protein, Kismet (Kis), regulates synaptic structure and function. Kis influences endocytosis, the localization of multiple synaptic proteins, neurotransmission, and memory in Drosophila. To better understand how Kis’ transcriptional activity regulates synaptic structure and function, we will first determine whether Kis exerts its synaptic effects by influencing key synaptic organizational proteins including Rab11 and its interacting proteins. Next, we will determine if Kis acts in unique protein complexes to affect transcription of genes important for synapse structure and function including appl, endoB, nlg2, and rab11. These experiments will provide valuable research experiences for Master’s and undergraduate students. They will also provide mechanistic insight to better uncover how chromatin remodeling regulates neurotransmission and protein localization thereby informing our understanding of synaptic physiology and pathology. Effective novel treatments for neurodevelopmental disorders and neurodegenerative diseases will require additional knowledge of how chromatin remodeling helps execute synaptic events.

染色质重塑蛋白在复合物中起作用，从而调节DNA的可及性，确定是否发生转录。染色质重塑对所有细胞都很重要，过程，但染色质重塑蛋白如何与或反对影响突触活性的其他蛋白质还没有被很好地理解。染色质重塑蛋白质，包括染色体结构域解旋酶结合结构域（CHD）蛋白质家族，涉及神经发育障碍、突触可塑性和神经变性疾病。拟议工作的目标是更好地了解CHD蛋白，Kismet（Kis），调节突触结构和功能。Kis影响内吞作用，突触蛋白、神经传递和果蝇的记忆。为了更好地了解基斯转录活性调节突触的结构和功能，我们将首先确定是否 Kis通过影响包括Rab11在内的关键突触组织蛋白发挥其突触效应及其相互作用的蛋白质。接下来，我们将确定Kis是否在独特的蛋白质复合物中起作用，影响对突触结构和功能重要的基因的转录，包括appl，endoB， NLG 2和Rab 11。这些实验将为硕士研究生提供宝贵的研究经验，本科生。他们还将提供机械的洞察力，以更好地揭示如何染色质重塑调节神经传递和蛋白质定位，从而告知我们，了解突触生理学和病理学。有效的新型治疗方法，神经发育障碍和神经退行性疾病将需要额外的知识染色质重塑如何帮助执行突触事件。