Investigating How Chromatin Remodeling Affects Endocytosis and Synaptic Organization

染色质重塑蛋白在复合体中起作用，从而调节DNA的可及性

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.