# Membrane Curvature Sensing Mechanisms for Synaptic Vesicle Endocytosis

> **NIH NIH R01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $485,941

## Abstract

Project Summary
Endocytosis plays a crucial role in supporting the health of the human brain. Functionally, synaptic vesicle
endocytosis allows neurons to sustain synaptic transmission without exhausting the supply of synaptic
vesicles. Structurally, endocytosis supports the maintenance of synapses and neural circuits. As a result,
defective synaptic vesicle endocytosis creates deficits in neurotransmission that underlie a wide spectrum of
neurological diseases and psychiatric disorders. The long-term goal of this study is to determine how endocytic
proteins act in concert to support diverse routes of endocytosis at synapses. Work from several laboratories
including my own has found that the curvature-sensing protein endophilin plays a critical role in synaptic
vesicle endocytosis. In this proposal, we will examine the hypothesis that curvature-sensing mechanisms guide
endocytic proteins to perform their function in various routes of endocytosis. We propose three Specific Aims.
1) We will determine the role of curvature-sensing motifs in vivo. We focus on the curvature-sensing
amphipathic helix of endophilin as it is essential for synaptic vesicle endocytosis. 2) We will study how
curvature signals are received by the downstream protein synaptojanin to support synaptic vesicle
endocytosis, and to prevent age-dependent decay of synaptic transmission. 3) We will determine the
mechanism of endophilin-independent endocytosis, an area that lacks molecular information. Through an
unbiased genetic screen, we have identified another curvature-sensing protein that acts in a parallel pathway
with endophilin. Results from these studies are expected to to push boundaries of current knowledge of
synaptic biology and to lead toward solutions for neurological disorders.

## Key facts

- **NIH application ID:** 9942235
- **Project number:** 1R01NS115974-01
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Jihong Bai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $485,941
- **Award type:** 1
- **Project period:** 2020-02-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9942235

## Citation

> US National Institutes of Health, RePORTER application 9942235, Membrane Curvature Sensing Mechanisms for Synaptic Vesicle Endocytosis (1R01NS115974-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9942235. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*