# Mechanisms of Ras signaling in single synapses

> **NIH NIH R01** · MAX PLANCK FLORIDA CORPORATION · 2023 · $566,899

## Abstract

ABSTRACT
The Ras superfamily of small GTPase proteins is important for many neuronal processes essential to synaptic
plasticity, including long-term synaptic potentiation, formation of new synapses, and regulation of cell excitability.
Among the Ras superfamily, a particularly important subfamily is a group of proteins called Rab, which regulate
trafficking of membrane and glutamate receptors during synaptic plasticity. Consistent with the importance of
Rab signaling in synaptic plasticity, abnormal Rab signaling is associated with diseases causing cognitive
impairments and learning deficits. However, the spatiotemporal dynamics of Rab proteins during synaptic
plasticity and their exact functions at individual dendritic spines are not fully understood. Thus, the objective of
this project is to elucidate the mechanisms and roles of Rab protiens in dendritic spines during synaptic plasticity.
We have developed highly sensitive biosensors for imaging activity of Rab4, Rab5, Rab8 and Rab10. Our
preliminary data suggest that Rab proteins are activated or inactivated in different temporal windows during
synaptic plasticity. Based on these preliminary data and previous literatures, our central hypothesis is that Rab
proteins regulate the balance of membrane trafficking between different internal membrane compartments in
dendritic spines to regulate functional and structural plasticity of dendritic spines, and this in turn modulates
synaptic plasticity, learning and memory. In this project, we will further analyze signaling mediated by Rab
proteins and their roles in trafficking of membrane and receptors during synaptic plasticity. Our specific aims are
1) to reveal the spatiotemporal dynamics of Rab activity during synaptic plasticity and to identify upstream
regulators of Rab proteins, 2) to elucidate the roles of Rab proteins in structure and function of spines and in
membrane trafficking during synaptic plasticity, 3) to identify the roles of Rab proteins in glutamate receptor
internalization and recycling using biochemical assays, and 4) to elucidate the roles of Rab proteins in synaptic
plasticity, learning and memory. This work will advance our understanding of how Rab couples calcium with
synaptic plasticity, learning and memory.

## Key facts

- **NIH application ID:** 10540322
- **Project number:** 5R01MH080047-15
- **Recipient organization:** MAX PLANCK FLORIDA CORPORATION
- **Principal Investigator:** Ryohei Yasuda
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $566,899
- **Award type:** 5
- **Project period:** 2007-04-05 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10540322

## Citation

> US National Institutes of Health, RePORTER application 10540322, Mechanisms of Ras signaling in single synapses (5R01MH080047-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10540322. Licensed CC0.

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