# Investigating How Chromatin Remodeling Affects Endocytosis and Synapse Organization

> **NIH NIH R15** · SOUTHERN ILLINOIS UNIV AT EDWARDSVILLE · 2020 · $68,725

## Abstract

Project Summary
The transmembrane protein β-amyloid precursor protein (APP) is central to the pathophysiology of Alzheimer’s
disease (AD). The β-amyloid hypothesis posits that aberrant processing of APP leads to the formation of β-
amyloid aggregates, which are neurotoxic leading to the cognitive impairments observed in AD. Despite the
importance of APP in AD, little is known about its function or how neurons regulate its expression. We have
found that Kismet (Kis), a chromatin remodeling protein in Drosophila, regulates expression of APP-like and
neuronal processes that are dysregulated in AD. Kis is similar to the mammalian chromatin helicase binding
domain (CHD) proteins CHD7 and CHD8, both of which are implicated in neurodevelopmental disorders
including CHARGE Syndrome and autism spectrum disorders, respectively, and synaptic function. The goal of
this proposal is to better understand how the epigenetic chromatin remodeling protein, Kis, regulates APP-like
expression in animals. Mutations in kis lead to increased levels of APP-like in neurons and of cell adhesion
molecules at the synapse. The latter are known to interact with APP and APP-like. We hypothesize that Kis
promotes synaptic function and organization by suppressing synaptic levels of APP-like thereby affecting the
recycling of synaptic vesicles. To test this hypothesis, we will first better characterize the functional interaction
between Kis and APP-like. Then we will determine whether Kis and APP-like work cooperatively to influence
synaptic vesicle endocytosis and localize cell adhesion molecules to the synapse. These data will help us better
understand how chromatin remodeling proteins enable synapse function and provide mechanistic insight into
the pathology of AD.

## Key facts

- **NIH application ID:** 10121448
- **Project number:** 3R15NS101608-01A1S1
- **Recipient organization:** SOUTHERN ILLINOIS UNIV AT EDWARDSVILLE
- **Principal Investigator:** FAITH L LIEBL
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $68,725
- **Award type:** 3
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10121448

## Citation

> US National Institutes of Health, RePORTER application 10121448, Investigating How Chromatin Remodeling Affects Endocytosis and Synapse Organization (3R15NS101608-01A1S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10121448. Licensed CC0.

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