# Sorting and Trafficking in the Endosomal System

> **NIH NIH R37** · YALE UNIVERSITY · 2021 · $404,599

## Abstract

Project Summary
The endosomal system is composed of a continuum of organelles that are derived by vesicle-mediated
trafficking from the plasma membrane and Golgi apparatus which mature until fusing with the lysosome.
Molecular sorting reactions that take place during endosome maturation direct molecules into the lysosomal
degradation pathway, or into pathways that export the molecules from the endosome for subsequent trafficking
to another organelle for re-use. The latter ‘endosomal recycling’ and ‘retrograde’ trafficking pathways provide a
key means for regulating the composition of the PM, and hence cellular identity, and of internal organelles in
response to metabolic and environmental cues. Importantly, genetic perturbations to these pathways result in
lysosomal storage diseases, Parkinson’s disease, Alzheimer’s disease, cancer, and other diseases, indicating
that proper sorting at the endosome is essential for protection from disease. The broad goal of this research
project is to elucidate the mechanisms by which proteins and lipids are sorted and trafficked from the
endosome. In previous funding cycles we discovered that Golgi-directed retrograde pathways are used to
modulate the composition of the plasma membrane in response to environmental and nutritional cues, and we
established roles for a soluble protein sorting complex called ‘retromer’ and effectors of phosphatidylinositol 3-
kinase, called sorting nexin proteins, in this process. These components function together to capture and
package integral membrane protein and lipid cargo into transport carriers that bud and fission from the
endosome. The proposed research will elucidate the mechanistic principles and events that underlie sorting of
integral membrane proteins and lipids within the endo-lysosomal system. Diverse experimental approaches will
be applied to identify and characterize regulatory mechanisms that control retromer-mediated sorting in cells,
and these will be complemented with biochemical reconstitution studies that will elucidate and order the
molecular functions of the components of retromer and associated proteins. Additional studies will elucidate
the functions and mechanistic principles of retromer-independent recycling pathways by sorting nexins.

## Key facts

- **NIH application ID:** 10224751
- **Project number:** 5R37GM061221-22
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Christopher G Burd
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $404,599
- **Award type:** 5
- **Project period:** 2000-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10224751

## Citation

> US National Institutes of Health, RePORTER application 10224751, Sorting and Trafficking in the Endosomal System (5R37GM061221-22). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10224751. Licensed CC0.

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