Related Experiment Video
Updated: Jun 23, 2026
10:39
Functional Manipulation of Maternal Gene Products Using In Vitro Oocyte Maturation in Zebrafish
Published on: April 22, 2017
11.5K
Gm364 coordinates MIB2/DLL3/Notch2 to regulate female fertility through AKT activation
Liang-Jian Chen1, Na-Na Zhang1,2, Chun-Xiang Zhou1,3
1State Key Lab of Reproductive Medicine, Nanjing Medical University, 101 Longmian Ave., Nanjing, 211166, Jiangsu, China.
Cell Death and Differentiation
|October 12, 2021
Summary
Gm364 protein is crucial for female fertility, regulating oocyte quality and development. Its absence leads to reduced follicle numbers and increased aneuploidy, impacting reproductive potential.
Area of Science:
- Reproductive Biology
- Molecular Endocrinology
- Cellular Signaling
Background:
- Integral membrane proteins coordinate receptor function in cellular microdomains.
- Gm364, a transmembrane protein, is implicated as a potential female fertility factor.
- Its precise role in female fertility remains uncharacterized.
Purpose of the Study:
- To elucidate the function of Gm364 in female fertility.
- To investigate the molecular mechanisms underlying Gm364's role in oocyte development and quality.
Main Methods:
- Global knockout of Gm364 in a mouse model.
- Assessment of ovarian follicle counts and oocyte quality parameters (ROS, γ-H2AX, mitochondrial membrane potential).
- Analysis of oocyte maturation, aneuploidy rates, and the Notch signaling pathway components.
Main Results:
- Gm364 knockout reduced primordial and growing follicles.
- Oocyte quality was impaired, evidenced by increased reactive oxygen species (ROS) and DNA damage (γ-H2AX).
- Mitochondrial function, maturation rates, and ploidy stability were compromised in Gm364-deficient oocytes.
Conclusions:
- Gm364 is essential for maintaining ovarian follicle reserve and oocyte quality.
- Gm364 regulates female fertility by anchoring MIB2, activating the DLL3-Notch2-NICD2-AKT signaling cascade.
- Disruption of this pathway impairs oocyte meiosis and quality, highlighting Gm364 as a critical regulator of female reproductive health.
Related Concept Videos
01:45Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
02:39Positive Regulator Molecules
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
02:15M-Cdk Drives Transition Into Mitosis
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
01:22PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...
01:16Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...