Microtubule poleward flux in human cells is driven by the coordinated action of four kinesins

Area of Science:

• Cell Biology
• Molecular Motors
• Mitosis

Background:

• Mitotic spindle microtubules (MTs) exhibit poleward flux, a process whose driving force and function in human cells are not fully understood.
• Understanding MT flux is critical for comprehending chromosome segregation and overall cell division accuracy.

Purpose of the Study:

• To elucidate the molecular mechanisms and identify the key motor proteins responsible for driving MT poleward flux in human cells.
• To investigate the functional significance of MT flux in regulating mitotic spindle length and dynamics.

Main Methods:

• Conducted loss-of-function screenings in human cells.
• Analyzed MT dynamics using advanced microscopy techniques.
• Investigated the roles of specific kinesin motor proteins (Kinesin-7/CENP-E, Kinesin-4/KIF4A, Kinesin-5/EG5, Kinesin-12/KIF15) and MT couplers (HSET, NuMA).

Main Results:

• Identified Kinesin-7/CENP-E as the primary driver of MT flux in early prometaphase, with Kinesin-4/KIF4A dominating in later stages.
• Demonstrated coordination between Kinesin-7/CENP-E, Kinesin-4/KIF4A, Kinesin-5/EG5, and Kinesin-12/KIF15.
• Established that MT flux rate correlates with spindle length and is essential for counteracting MT depolymerization mediated by Kinesin-13/MCAK.

Conclusions:

• Unveiled a coordinated mechanism involving four kinesins that drives MT poleward flux in human cells.
• Showed that MT flux is essential for regulating mitotic spindle length by balancing MT polymerization and depolymerization.
• Provided insights into the transmission of forces from non-kinetochore MTs to kinetochore MTs via MT couplers.