# ANALYSIS OF ESCRT FUNCTION IN ENDOLYSOSOMAL TRAFFICKING

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $82,150

## Abstract

Abstract
The endolysosomal network is the portal by which extracellular material enters the cell. As such, the
membranes of the endosomes, phagosomes, and lysosomes that comprise this network face challenges from
pathogens and other internalized materials as well as from metabolic and chemical stresses. Consequences of
damage vary according to the specific compartment and degree of damage, but extensive lysosomal
membrane permeabilization triggers cell death while limited disruption of endosomes and phagosomes by
particulate material and pathogens leads to inflammasome activation and ensuing cytokine responses. A
widely deployed strategy for removing damaged organelles involves the use of selective autophagy, referred to
as lysophagy. Removal is, however, unnecessary if organelles are instead repaired. We recently discovered a
new role for the ESCRT (endosomal sorting complex required for transport) machinery in responding to nano-
scale disruptions in endolysosomal membranes and promoting their repair.
In this project, we are building on this discovery and testing the hypothesis that ESCRTs (and in particular
ESCRT-III proteins) play a key role in maintaining endolysosomal integrity and function by recognizing and
repairing nanoscale membrane damage. This role for the ESCRT machinery is distinct from its widely
recognized function in intralumenal vesicle biogenesis and appears applicable at both the plasma membrane
and on internal organelles. Nanoscale damage involves short-lived nm-size pre-pore or pore(s) that reseal or,
above a critical threshold, expand to allow unrestrained content exchange. We are using a range of chemical,
physical, and biological stressors to define the signals as well as molecular and physical mechanisms
underlying ESCRT-mediated repair. The equipment requested in this administrative supplement application will
allow us to upgrade our existing CSU-W1 spinning disc confocal microscope system to provide uniform laser
illumination along with rapid and precise photomanipulation of fluorescently tagged molecules as they respond
to and protect cells from endolysosomal membrane stress. This enhanced control of illumination will enable the
quantitative analyses needed to complete this project and provide insights into how ESCRTs and cooperating
molecules sense and respond to a broad range of physiologic and pathophysiologic membrane stress.

## Key facts

- **NIH application ID:** 10683489
- **Project number:** 3R01GM122434-06S1
- **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:** 2022
- **Award amount:** $82,150
- **Award type:** 3
- **Project period:** 2017-01-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10683489

## Citation

> US National Institutes of Health, RePORTER application 10683489, ANALYSIS OF ESCRT FUNCTION IN ENDOLYSOSOMAL TRAFFICKING (3R01GM122434-06S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10683489. Licensed CC0.

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