NuSAP modulates the dynamics of kinetochore microtubules by attenuating MCAK depolymerisation activity

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Nucleolar and spindle-associated protein (NuSAP) is a microtubule-associated protein crucial for mitosis.
• NuSAP functions as a microtubule stabilizer, but its precise role in regulating mitotic progression is not fully understood.

Purpose of the Study:

• To elucidate the mechanism by which NuSAP regulates mitosis.
• To identify novel binding partners of NuSAP and characterize their functional interactions.

Main Methods:

• Co-immunoprecipitation to identify binding partners.
• In vitro assays to assess microtubule dynamics and depolymerization activity.
• Site-directed mutagenesis and kinase assays to investigate phosphorylation effects.

Main Results:

• Mitotic centromere-associated kinesin (MCAK), a microtubule depolymerase, was identified as a novel binding partner of NuSAP.
• NuSAP modulates the dynamics and depolymerization activity of MCAK.
• Phosphorylation of MCAK by Aurora B kinase enhances NuSAP-MCAK interaction and affects MCAK activity.

Conclusions:

• NuSAP regulates kinetochore microtubule dynamics by modulating MCAK depolymerization activity in an Aurora B kinase-dependent manner.
• This interaction provides new insights into NuSAP's function in spindle assembly during mitosis.
• The findings reveal a novel regulatory pathway controlling microtubule dynamics essential for accurate chromosome segregation.