Related Experiment Video
Updated: May 12, 2025
09:52
A Fluorescence-based Assay of Phospholipid Scramblase Activity
Published on: September 20, 2016
13.8K
Phospholipid flippase ATP11A brokers uterine epithelial integrity and function
Alexa Krala1,2, Aleksandra O Tsolova1,2, Bethany N Radford1,2
1Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Summary
Genetic ablation of the membrane lipid flippase ATP11A in mice causes uterine dysfunction, impacting embryo implantation and leading to pregnancy failure. Loss of ATP11A also increases placental and heart defects in embryos.
Area of Science:
- Reproductive Biology
- Cell Biology
- Developmental Biology
Background:
- Steroid hormones like estrogen and progesterone are crucial for uterine adaptations necessary for embryo implantation and successful pregnancy.
- The uterine epithelium undergoes significant hormonal regulation to prepare for pregnancy.
Purpose of the Study:
- To investigate the role of the membrane lipid flippase ATP11A in uterine function and its impact on female reproductive success.
- To elucidate the cellular and molecular mechanisms underlying uterine receptivity deficits caused by ATP11A deficiency.
Main Methods:
- Genetic ablation of the *Atp11a* gene in mice to create *Atp11a*-null models.
- Analysis of uterine epithelial cell morphology, tight junction integrity, and gene expression profiles.
- Assessment of uterine gland progenitor cell populations.
- Evaluation of embryo implantation rates, placental development, and incidence of congenital heart defects.
Main Results:
- *Atp11a* ablation in uterine epithelial cells leads to severe morphological and transcriptional defects, including loss of tight junctions and incomplete luminal epithelial cell specification.
- Uterine glands in *Atp11a*-null females show depletion of key progenitor cells (SOX9, PAX8, LGR5, PROM1).
- Mice with *Atp11a* deficiency exhibit uterine receptivity deficits, resulting in frequent pregnancy failures.
- Even heterozygous loss of *Atp11a* function increases abnormal placental trophoblast differentiation and developmental heart defects in wild-type embryos.
Conclusions:
- ATP11A is essential for maintaining uterine epithelial integrity and hormonal responsiveness, critical for successful pregnancy.
- Disruptions in maternal uterine function due to *Atp11a* loss have significant consequences for embryo development, including placental and cardiac abnormalities.
- These findings underscore the critical role of the maternal genotype in reproductive outcomes and the etiology of developmental disorders.
More Related Videos
08:49Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
Published on: March 14, 2021
3.9K
10:52Radiolabeling and Quantification of Cellular Levels of Phosphoinositides by High Performance Liquid Chromatography-coupled Flow Scintillation
Published on: January 6, 2016
10.3K
Related Concept Videos
01:19Membrane Asymmetry Regulating Transporters
4.2K
Enzymes like flippase, floppase, and scramblase transfer phospholipids from one layer to another in the membrane, thereby affecting membrane asymmetry.
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
4.2K
01:42Phosphoinositides and PIPs
7.2K
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
7.2K
01:26Membrane Fluidity
10.7K
Membrane fluidity is explained by the fluid mosaic model of the cell membrane, which describes the plasma membrane structure as a mosaic of components—including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character.
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...
10.7K
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.2K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
01:28Assembly of the Lipid Bilayer in the ER
3.1K
Biological membranes are more than just a barrier separating cell cytoplasm from the outside environment. They are highly dynamic and help maintain the integrity and physiological stability of the cells as well as membrane-bound organelles. Membranes also play vital roles in cell-to-cell and intracellular communication.
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between...
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between...
3.1K
01:39Mechanism of Filopodia Formation
2.2K
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.2K