Reversible arginine methylation of PI3KC2α controls mitotic spindle dynamics
Yena Cho1,2, Jee Won Hwang2, Mark T Bedford3
1Muscle Physiome Research Center, Research Institute of Pharmaceutical Sciences, Sookmyung Women's University, Seoul, 04310, Republic of Korea.
Cell Communication and Signaling : CCS
|October 2, 2025
Summary
Phosphatidylinositol 3-kinase class 2α (PI3KC2α) regulates microtubule dynamics. Its methylation by CARM1 stabilizes microtubules, while KDM4A demethylation is controlled by PKC during mitosis for spindle formation.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Microtubules are essential for cell structure and function, relying on dynamic polymerization of αβ-tubulin dimers.
- Regulation of microtubule dynamics is crucial for cellular processes, particularly during cell division.
Purpose of the Study:
- To identify novel regulatory factors involved in microtubule dynamics.
- To elucidate the role of phosphatidylinositol 3-kinase class 2α (PI3KC2α) in microtubule regulation.
- To investigate the impact of post-translational modifications on PI3KC2α function and microtubule stability.
Main Methods:
- Investigated the interaction between PI3KC2α and α-tubulin.
- Utilized biochemical assays to study the methylation and demethylation of PI3KC2α.
- Examined the role of coactivator-associated arginine methyltransferase 1 (CARM1) and lysine demethylase 4A (KDM4A) in regulating PI3KC2α.
- Analyzed the effect of protein kinase C (PKC)-mediated phosphorylation on KDM4A activity during mitosis.
Main Results:
- Discovered PI3KC2α as a novel regulator of microtubule dynamics.
- Asymmetric dimethylation of PI3KC2α at R175 (R175me2a) by CARM1 enhances its interaction with α-tubulin, stabilizing microtubules.
- KDM4A acts as an arginine demethylase for PI3KC2α R175me2a.
- PKC-mediated phosphorylation of KDM4A during mitosis causes its dissociation from PI3KC2α, maintaining R175me2a levels and facilitating spindle formation.
Conclusions:
- Reversible arginine methylation of PI3KC2α is critical for regulating mitotic spindle dynamics.
- The coordinated action of CARM1 and KDM4A modulates microtubule behavior via PI3KC2α R175 methylation.
- These findings provide new insights into the regulatory mechanisms governing mitotic progression and microtubule stability.
Related Concept Videos
02:19The Spindle Assembly Checkpoint
3.7K
The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
3.7K
02:17Separation of Sister Chromatids
4.4K
At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
At the onset of anaphase, separase, a proteolytic enzyme, is...
4.4K
02:50Spindle Assembly
4.2K
Spindle assembly occurs through three, often coexisting, pathways – the centrosome-mediated pathway, the chromatin-mediated pathway, and the microtubule-mediated pathway – collectively contributing to form a robust spindle apparatus.
In most cells, centrosomes are the primary microtubule nucleation centers. In the centrosome-mediated pathway, the G2-prophase transition triggers centrosome maturation and increased microtubule nucleation. Progressive nucleation results in a...
In most cells, centrosomes are the primary microtubule nucleation centers. In the centrosome-mediated pathway, the G2-prophase transition triggers centrosome maturation and increased microtubule nucleation. Progressive nucleation results in a...
4.2K
02:15M-Cdk Drives Transition Into Mitosis
6.3K
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...
6.3K
01:22PI3K/mTOR/AKT Signaling Pathway
5.4K
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...
5.4K
02:02Meiosis II
49.0K
Meiosis II entails cell division and segregation of the sister chromatids, resulting in the production of four unique haploid gametes. The steps for meiosis II are similar to mitosis, except that meiosis II occurs in haploid cells, whereas mitosis occurs in diploid cells.
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
49.0K