# ANALYSIS OF ESCRT FUNCTION IN ENDOLYSOSOMAL TRAFFICKING

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $382,861

## Abstract

The Endosomal Sorting Complex Required for Transport (ESCRT) machinery is a set of interacting protein
complexes responsible for cargo selection and biogenesis of intralumenal vesicles inside endosomal
multivesicular bodies, also known as late endosomes. Evolutionary conservation and the discovery that
ESCRTs are required for topologically equivalent processes including viral budding, cytokinetic abscission,
and nuclear envelope closure led to the now widely accepted concept that ESCRTs are uniquely involved in
membrane fission for reactions that share this topology. ESCRT-III proteins act by changing conformation
and polymerizing into membrane-remodeling filaments that spiral on the inside – negatively curved –
surface of membrane tubules, ultimately pulling the tubules closed to drive membrane fission and release.
Intriguingly, there are twelve ESCRT-III proteins in humans that are not functionally interchangeable.
Beyond identification of different molecular binding partners, there has been little structural distinction
among these proteins to explain their unique physiological importance. We recently made the surprising
discovery that two human ESCRT-III proteins – CHMP1B and IST1 – assemble into filaments that spiral
around the outside – positively curved – surface of membrane tubules, forming external coats in vitro and in
vivo. This unexpected preference for positively curved membrane tubules challenges the dogma that the
membrane deforming and fission activity associated with ESCRT-III filaments is limited to a single topology
and prompts us to reconsider established paradigms for ESCRT-III function. This project will (1) define the
topology preference of particular ESCRT-III homo- and heteropolymers polymers and the corresponding
distribution of endogenous ESCRT-III proteins across the endosomal system, (2) establish the role(s) of
representative ESCRT-III proteins in distinct endosomal cargo trafficking pathways, and (3) compare the
effects of depleting different ESCRT-III proteins on endosomal and lysosomal morphology. This work will
expand our understanding of the ESCRT-III membrane remodeling system with significant implications for
future studies of trafficking and organization within the endolysosomal system.

## Key facts

- **NIH application ID:** 9872173
- **Project number:** 5R01GM122434-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Phyllis I Hanson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $382,861
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872173

## Citation

> US National Institutes of Health, RePORTER application 9872173, ANALYSIS OF ESCRT FUNCTION IN ENDOLYSOSOMAL TRAFFICKING (5R01GM122434-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9872173. Licensed CC0.

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