A Non-Motor Microtubule Binding Site Is Essential for the High Processivity and Mitotic Function of Kinesin-8 Kif18A

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2011
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Storch, Marko
Howard, Jonathon
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PLoS ONE. 2011, 6(11), e27471. eISSN 1932-6203. Available under: doi: 10.1371/journal.pone.0027471
Zusammenfassung

BACKGROUND:

Members of the kinesin-8 subfamily are plus end-directed molecular motors that accumulate at the plus-ends of kinetochore-microtubules (kt-MTs) where they regulate MT dynamics. Loss of vertebrate kinesin-8 function induces hyperstable MTs and elongated mitotic spindles accompanied by severe chromosome congression defects. It has been reported that the motility of human kinesin-8, Kif18A, is required for its accumulation at the plus tips of kt-MTs.

METHODOLOGY/FINDINGS:

Here, we investigate how Kif18A localizes to the plus-ends of kt-MTs. We find that Kif18A lacking its C-terminus does not accumulate on the tips of kt-MTs and fails to fulfill its mitotic function. In vitro studies reveal that Kif18A possesses a non-motor MT binding site located within its C-proximal 121 residues. Using single molecule measurements we find that Kif18A is a highly processive motor and, furthermore, that the C-terminal tail is essential for the high processivity of Kif18A.

CONCLUSION/SIGNIFICANCE:

These results show that Kif18A like its yeast orthologue is a highly processive motor. The ability of Kif18A to walk on MTs for a long distance without dissociating depends on a non-motor MT binding site located at the C-terminus of Kif18A. This C-proximal tail of Kif18A is essential for its plus-end accumulation and mitotic function. These findings advance our understanding of how Kif18A accumulates at the tips of kt-MTs to fulfill its function in mitosis.

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Fachgebiet (DDC)
570 Biowissenschaften, Biologie
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Kif18A, KInesin, Microtubule, Mitose, Chromosomenbande Zellteilung, Mikrotubuli, Kinesin
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ISO 690MAYR, Monika, Marko STORCH, Jonathon HOWARD, Thomas U. MAYER, 2011. A Non-Motor Microtubule Binding Site Is Essential for the High Processivity and Mitotic Function of Kinesin-8 Kif18A. In: PLoS ONE. 2011, 6(11), e27471. eISSN 1932-6203. Available under: doi: 10.1371/journal.pone.0027471
BibTex
@article{Mayr2011NonMo-17239,
  year={2011},
  doi={10.1371/journal.pone.0027471},
  title={A Non-Motor Microtubule Binding Site Is Essential for the High Processivity and Mitotic Function of Kinesin-8 Kif18A},
  number={11},
  volume={6},
  journal={PLoS ONE},
  author={Mayr, Monika and Storch, Marko and Howard, Jonathon and Mayer, Thomas U.},
  note={Article Number: e27471}
}
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