Abstract
Mitotic chromosome segregation is orchestrated by the dynamic interaction of spindle microtubules with the kinetochores. During chromosome alignment, kinetochore-bound microtubules undergo dynamic cycles between growth and shrinkage, leading to an oscillatory movement of chromosomes along the spindle axis. Although kinetochore protein CENP-H serves as a molecular control of kinetochore-microtubule dynamics, the mechanistic link between CENP-H and kinetochore microtubules (kMT) has remained less characterized. Here, we show that CSPP1 is a kinetochore protein essential for accurate chromosome movements in mitosis. CSPP1 binds to CENP-H in vitro and in vivo. Suppression of CSPP1 perturbs proper mitotic progression and compromises the satisfaction of spindle assembly checkpoint. In addition, chromosome oscillation is greatly attenuated in CSPP1-depleted cells, similar to what was observed in the CENP-H-depleted cells. Importantly, CSPP1 depletion enhances velocity of kinetochore movement, and overexpression of CSPP1 decreases the speed, suggesting that CSPP1 promotes kMT stability during cell division. Specific perturbation of CENP-H/CSPP1 interaction using a membrane-permeable competing peptide resulted in a transient mitotic arrest and chromosome segregation defect. Based on these findings, we propose that CSPP1 cooperates with CENP-H on kinetochores to serve as a novel regulator of kMT dynamics for accurate chromosome segregation.
Highlights
Kinetochore microtubule dynamics orchestrate proper chromosome movement in mitosis
The kinetochore localization of centrosome and spindle pole-associated protein 1 (CSPP1) decreases once chromosome alignment is achieved, the kinetochore localization of GFP-CSPP1 is still visible in metaphase cells with moderate expression levels, despite the background from strong decoration of spindle MTs (Fig. 1B)
Proper chromosome oscillation and kinetochore microtubules (kMT) dynamics is required for accurate chromosome segregation
Summary
Kinetochore microtubule dynamics orchestrate proper chromosome movement in mitosis. Results: CSPP1 is a novel kinetochore protein that regulates chromosome oscillation during cell division. Conclusion: CSPP1 associates with CENP-H to control chromosome oscillation by regulating kinetochore microtubule dynamics. Mitotic chromosome segregation is orchestrated by the dynamic interaction of spindle microtubules with the kinetochores. We show that CSPP1 is a kinetochore protein essential for accurate chromosome movements in mitosis. Specific perturbation of CENP-H/CSPP1 interaction using a membranepermeable competing peptide resulted in a transient mitotic arrest and chromosome segregation defect. Based on these findings, we propose that CSPP1 cooperates with CENP-H on kinetochores to serve as a novel regulator of kMT dynamics for accurate chromosome segregation
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