# Massive Cardiac Endocytosis and Ectosome Shedding

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $405,000

## Abstract

ABSTRACT
This project focuses on cardiac signaling pathways in which lipid metabolism, coupled to
mitochondrial activity state, promote massive sarcolemma internalization via endocytosis
(MEND) and/or massive ectosome shedding (MESS) to the extracellular space. The
endocytosis pathway depends on fatty acid metabolism and the generation of
cytoplasmic acyl-coenzyme A that is used to lipidate numerous sarcolemmmal proteins.
The shedding pathway depends primarily on the generation of lysophosphatidylcholine,
the activation of its receptors in the cardiac myocyte, and subsequent scrambling of
sarcolemmal phospholipids between monolayers. Both mechanisms appear to depend
on the generation of ordered membrane domains within the sarcolemma which then
facilitate unique protein-protein interactions and functions. Both mechanisms are
expected to play major roles in membrane remodeling that occurs in
ischemia/reperfusion injury, as well as in major chronic, degenerative diseases involving
oxidative stress. Using multiple mice lines with deficiencies in these pathways, as well as
drugs to manipulate individual reactions, we will analyze the commonalities and
distinctive traits of these pathways, identify the essential molecular players, factors that
decisively push the sarcolemma to MEND or MESS, and define more precisely the
physiological and pathological roles of MEND and MESS. The project will provide insight
into fundamental cell regulatory mechanisms that have a high impact for an
understanding of the leading causes of death in the developed world.

## Key facts

- **NIH application ID:** 10147135
- **Project number:** 5R01HL119843-08
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** DONALD W HILGEMANN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $405,000
- **Award type:** 5
- **Project period:** 2014-04-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10147135

## Citation

> US National Institutes of Health, RePORTER application 10147135, Massive Cardiac Endocytosis and Ectosome Shedding (5R01HL119843-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10147135. Licensed CC0.

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