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Updated: Mar 19, 2026

Directly Measuring Forces Within Reconstituted Active Microtubule Bundles
Published on: May 10, 2022
DDA3 and Mdp3 modulate Kif2a recruitment onto the mitotic spindle to control minus-end spindle dynamics
Hye Jin Kwon1, Ji Eun Park1, Haiyu Song1
1Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
Abstract:
Active turnover of spindle microtubules (MTs) for the formation of a bi-orientated spindle, chromosome congression and proper chromosome segregation is regulated by MT depolymerases such as the kinesin-13 family and the plus-end-tracking proteins (+TIPs). However, the control mechanisms underlying the spindle MT dynamics that are responsible for poleward flux at the minus end of MTs are poorly understood. Here, we show that Mdp3 (also known as MAP7D3) forms a complex with DDA3 (also known as PSRC1) and controls spindle dynamics at the minus end of MTs by inhibiting DDA3-mediated Kif2a recruitment to the spindle. Aberrant Kif2a activity at the minus end of spindle MTs in Mdp3-depleted cells decreased spindle stability and resulted in unaligned chromosomes in metaphase, lagging chromosomes in anaphase, and chromosome bridges in telophase and cytokinesis. Although they play opposing roles in minus-end MT dynamics, acting as an MT destabilizer and an MT stabilizer, respectively, DDA3 and Mdp3 did not affect the localization of each other. Thus, the DDA3 complex orchestrates MT dynamics at the MT minus end by fine-tuning the recruitment of Kif2a to regulate minus-end MT dynamics and poleward MT flux at the mitotic spindle.
Insights
Mdp3 protein complexes with DDA3 to regulate microtubule (MT) dynamics at the mitotic spindle minus-end. This interaction fine-tunes Kif2a recruitment, ensuring proper chromosome segregation during cell division.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Microtubule (MT) dynamics are crucial for cell division, regulated by depolymerases and plus-end-tracking proteins (+TIPs).
- Mechanisms controlling MT dynamics at the minus-end, particularly poleward flux, remain incompletely understood.
Purpose of the Study:
- To investigate the role of Mdp3 (MAP7D3) in regulating spindle MT dynamics at the minus-end.
- To elucidate the interaction between Mdp3 and DDA3 (PSRC1) in controlling MT dynamics and chromosome segregation.
Main Methods:
- Depletion of Mdp3 in cells.
- Analysis of spindle MT stability and dynamics.
- Assessment of chromosome alignment and segregation.
- Immunofluorescence microscopy to determine protein localization.
Main Results:
- Mdp3 forms a complex with DDA3 and inhibits DDA3-mediated Kif2a recruitment to the spindle minus-end.
- Mdp3 depletion leads to aberrant Kif2a activity, decreased spindle stability, and chromosome segregation errors.
- DDA3 and Mdp3 do not affect each other's localization despite opposing roles in MT dynamics.
Conclusions:
- The DDA3-Mdp3 complex orchestrates MT minus-end dynamics by fine-tuning Kif2a recruitment.
- This regulation is essential for maintaining spindle stability, poleward MT flux, and accurate chromosome segregation during mitosis.
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