1. DDA3 and Mdp3 modulate Kif2a recruitment onto the mitotic spindle to control minus-end spindle dynamics
- Author
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Chang-Young Jang, Ji Eun Park, Haiyu Song, and Hye Jin Kwon
- Subjects
0301 basic medicine ,Kinesins ,Mitosis ,Spindle Apparatus ,Biology ,Microtubules ,Spindle pole body ,Polymerization ,Chromosome segregation ,03 medical and health sciences ,Chromosomes, Human ,Humans ,Kinetochores ,Metaphase ,Anaphase ,Kinetochore ,Cell Biology ,Phosphoproteins ,Cell biology ,Spindle apparatus ,Spindle checkpoint ,030104 developmental biology ,Microtubule-Associated Proteins ,Cytokinesis ,HeLa Cells ,Protein Binding - 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.
- Published
- 2015