# Coordination of intracellular trafficking pathways by Ypt/Rab GTPases and their GEFs

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $399,750

## Abstract

Abstract
Ypt/Rab GTPases together with their activators, guanine-nucleotide exchange factors (GEFs), have emerged
as key regulators of the multiple intracellular trafficking pathways. These pathways, in which proteins and
membranes are transported between intracellular compartments, are vital for the proper functioning of all
eukaryotic cells. Whereas the regulation of individual transport steps has been studied extensively, less is
known about their coordination. Our long-term goal is to elucidate how Ypt/Rab GTPases and their GEFs
coordinate individual transport steps in the same pathway and in different pathways. Landmark discoveries
about the mechanisms and machinery that underlie intracellular trafficking were made in yeast and shown to
pertain to humans. Therefore, we will continue to use yeast as a model to address these complicated issues,
because it allows easy utilization of sophisticated genetic approaches in combination with molecular and
cellular methods. Furthermore, the relatively small number of players (e.g., 11 Ypts in yeast versus ~70 Rabs
in humans) and the resultant simplified interaction networks make yeast an excellent model for studying the
coordination of transport steps, as planned here.
In this proposal, we will address this major question: How do different GEF complexes coordinate the
multiple functions of Ypt1 in the secretory and autophagy pathways? In the secretory pathway, cargo is
delivered from the endoplasmic reticulum to the plasma membrane through the Golgi apparatus. In the
constitutive and stress-induced autophagy pathways, excess or damaged cellular components are shuttled
for degradation in the lysosome through autophagosomes. The use of shared (Ypt1) or overlapping (TRAPP
GEFs) regulators leads us to propose that specificity in traffic outcomes (destinations) is achieved via the use
of specific TRAPPs, while coordination between pathways is achieved via use of a common GTPase, Ypt1.
The following specific questions will be addressed here: 1) How do two different TRAPP complexes
coordinate Ypt-mediated progression through the Golgi in the secretory pathway? 2) How do multiple
TRAPP complexes coordinate the function of Ypt1 in the secretory pathway and conserved selective
autophagy pathways? Based on our previous studies, we developed working hypotheses for Ypt/Rab
coordination, and will employ a combination of genetic, cellular and biochemical approaches to test them.
This study is highly relevant to human health because multiple essential processes, such as secretion of
hormones, presentation of receptors on the outer-cell membrane, internalization of ligands and receptors,
and response to stress, depend on efficient and well-coordinated intracellular trafficking. Therefore,
impairment of trafficking affects every system in the human body, including the development and functioning
of the brain, heart, and immune system. Homologs of the yeast regulators, which we propose to study here,
were implicated dire...

## Key facts

- **NIH application ID:** 9878678
- **Project number:** 5R01GM045444-26
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Nava Segev
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $399,750
- **Award type:** 5
- **Project period:** 1992-02-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878678

## Citation

> US National Institutes of Health, RePORTER application 9878678, Coordination of intracellular trafficking pathways by Ypt/Rab GTPases and their GEFs (5R01GM045444-26). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9878678. Licensed CC0.

---

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