Investigating How Chromatin Remodeling Affects Endocytosis and Synaptic Organization

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。

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.