A Phosphorylation Switch Governs KIF11's Mechanical Output During Mitosis
Amila Šemić1, Babu J N Reddy2,3, Joseph M Muretta4
1Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT 05405.
Biorxiv : the Preprint Server for Biology
|February 6, 2026
Summary
Src-family kinases phosphorylate kinesin-5 (KIF11) at Y211, impacting its motor function. This phosphorylation acts as a rheostat, tuning KIF11
Area of Science:
- Cell Biology
- Molecular Motors
- Cancer Biology
Background:
- Kinesin-5 (KIF11) motor protein is essential for mitotic spindle assembly and chromosome segregation.
- Src-family kinases phosphorylate KIF11, but the functional impact on its mechanochemistry is poorly understood.
Purpose of the Study:
- To investigate the mechanistic role of KIF11 phosphorylation at tyrosine 211 (Y211) in regulating motor function and spindle dynamics.
- To elucidate how Src-mediated phosphorylation of KIF11 influences mitotic force generation and spindle assembly.
Main Methods:
- Biochemical and biophysical assays, including optical trapping and Förster resonance energy transfer (FRET).
- Cellular assays using phospho-mimetic (Y211E) and non-phosphorylatable (Y211F) KIF11 mutants in human cells.
- Fluorescence recovery after photobleaching (FRAP) to assess motor turnover on microtubules.
Main Results:
- Y211 phosphorylation significantly slows KIF11 neck-linker docking, reducing motor velocity and force generation under load.
- Expression of Y211E impairs bipolar spindle formation and decreases spindle pole separation velocity in human cells.
- Y211F mutation shortens steady-state spindle length, and Y211E accelerates motor turnover on spindle microtubules, indicating heightened load sensitivity.
Conclusions:
- Src-mediated phosphorylation at Y211 acts as a rheostat, fine-tuning KIF11 mechanochemistry and spindle assembly dynamics.
- This phosphorylation links cancer-relevant Src kinase signaling to the regulation of mitotic force generation.
- Understanding KIF11 phosphorylation provides insights into mitotic regulation and potential therapeutic targets in cancer.
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