Reference: Thomas EC and Moore JK (2025) Selective regulation of kinesin-5 function by beta-tubulin carboxy-terminal tails. J Cell Biol 224(3).

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Abstract


The tubulin code hypothesis predicts that tubulin tails create programs for selective regulation of microtubule-binding proteins, including kinesin motors. However, the molecular mechanisms that determine selective regulation and their relevance in cells are poorly understood. We report selective regulation of budding yeast kinesin-5 motors by the beta-tubulin tail. Cin8, but not Kip1, requires the beta-tubulin tail for recruitment to the mitotic spindle, creating a balance of both motors in the spindle and efficient mitotic progression. We identify a negatively charged patch in the beta-tubulin tail that mediates interaction with Cin8. Using in vitro reconstitution with genetically modified yeast tubulin, we demonstrate that the charged patch of beta-tubulin tail increases Cin8 plus-end-directed velocity and processivity. Finally, we determine that the positively charged amino-terminal extension of Cin8 coordinates interactions with the beta-tubulin tail. Our work identifies a molecular mechanism underlying selective regulation of closely related kinesin motors by tubulin tails and how this regulation promotes proper function of the mitotic spindle.

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Thomas EC, Moore JK
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