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Processive Kinesin-14 HSET Exhibits Directional Flexibility Depending on Motor Traffic
Dana N Reinemann1, Stephen R Norris2, Ryoma Ohi3
1Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN 37235, USA.
Current Biology : CB
|July 19, 2018
Summary
The kinesin-14 HSET motor protein is processive and regulates spindle forces by acting as a brake against kinesin-5 Eg5, aiding in cell division. This research clarifies HSET
Area of Science:
- Cell Biology
- Biophysics
- Molecular Motors
Background:
- Cancer cells with extra centrosomes often form multipolar spindles.
- Minus-end-directed motor proteins like HSET and dynein resolve these into bipolar structures.
- HSET is thought to oppose Eg5 to balance spindle forces, but its mechanism was unclear.
Purpose of the Study:
- To elucidate the biomechanics of force generation by the kinesin-14 HSET motor.
- To understand HSET's role in antagonizing kinesin-5 Eg5 during spindle assembly.
Main Methods:
- Optical trapping to measure single HSET motor force generation.
- In vitro polarity-marked bundle assays to assess force generation on microtubules.
- Investigating HSET-Eg5 interactions at varied concentrations.
Main Results:
- Single HSET motors are processive, capable of multiple steps and bidirectional movement.
- HSET has a weak stall force (1.1 pN) and requires its tail domain for long-range motility.
- HSET generates force on anti-parallel microtubule bundles and acts as a force brake against Eg5, requiring a 10-fold higher Eg5 concentration to overcome.
Conclusions:
- HSET functions as a processive motor and force regulator in the mitotic spindle.
- HSET's ability to act as a brake is crucial for balancing spindle forces and ensuring bipolar geometry.
- HSET contributes to minus-end focusing and overall spindle stability.
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