# P4-ATPase mechanism of phospholipid translocation

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2020 · $339,855

## Abstract

Phospholipid asymmetry is a fundamental feature of the eukaryotic cell plasma membrane. The
aminophospholipids phosphatidylserine (PS) and phosphatidylethanolamine (PE) are restricted to the cytosolic
leaflet of the plasma membrane while sphingolipids and phosphatidylcholine are enriched in the extracellular
leaflet. Regulated exposure of PS and PE on the extracellular leaflet contributes to cell signaling, cytokinesis,
blood clotting, apoptotic cell corpse removal and host-viral interactions. Phospholipid asymmetry is established
by type IV P-type ATPases (P4-ATPases), a large family of flippases that pump aminophospholipids from the
exofacial leaflet to the cytosolic leaflet of the membrane bilayer. The P4-ATPase subfamily is highly conserved
among eukaryotes and these pumps have been implicated in pathological conditions such as obesity and type
2 diabetes, intrahepatic cholestasis, progressive hearing loss, immune deficiency, mental disability, hepatic
cancer and male infertility. In addition to their role in establishing membrane asymmetry, P4-ATPases are also
critical components of the vesicle-mediated protein trafficking machinery within the Golgi and endosomal
system. Through their role in protein trafficking, the P4-ATPases could have a strong influence on type 2
diabetes and insulin resistance, as well as the downregulation of growth factor receptors needed to prevent the
uncontrolled cell growth that is characteristic of cancer. The proposed studies will define how the P4-ATPases
establish membrane asymmetry and will be invaluable to our understanding of the pathologies associated with
P4-ATPase deficiencies.

## Key facts

- **NIH application ID:** 9853802
- **Project number:** 5R01GM107978-07
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** TODD R GRAHAM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $339,855
- **Award type:** 5
- **Project period:** 2013-09-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853802

## Citation

> US National Institutes of Health, RePORTER application 9853802, P4-ATPase mechanism of phospholipid translocation (5R01GM107978-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9853802. Licensed CC0.

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