Kif18B is a newly discovered plus-tip-tracking protein that is enriched on astral microtubule (MT) ends during early mitosis. Kif18B binds directly to EB1, and this interaction is required for proper localization of Kif18B and to control astral MT length.

During mitosis, the mitotic spindle is assembled to align chromosomes at the spindle equator in metaphase, and to separate the genetic material equally to daughter cells in anaphase. The spindle itself is a macromolecular machine composed of an array of dynamic microtubules and associated proteins that coordinate the diverse events of mitosis. Among the microtubule associated proteins are a plethora of molecular motor proteins that couple the energy of ATP hydrolysis to force production. These motors, including members of the kinesin superfamily, must function at the right time and in the right place to insure the fidelity of mitosis. Misregulation of mitotic motors in disease states, such as cancer, underlies their potential utility as targets for antitumor drug development and highlights the importance of understanding the molecular mechanisms for regulating their function. Here, we focus on recent progress about regulatory mechanisms that control the proper function of mitotic kinesins and highlight new findings that lay the path for future studies.

Proper regulation of microtubules (MTs) is critical for the execution of diverse cellular processes, including mitotic spindle assembly and chromosome segregation. There are a multitude of cellular factors that regulate the dynamicity of MTs and play critical roles in mitosis. Members of the Kinesin-8 family of motor proteins act as MT-destabilizing factors to control MT length in a spatially and temporally regulated manner. In this review, we focus on recent advances in our understanding of the structure and function of the Kinesin-8 motor domain, and the emerging contributions of the C-terminal tail of Kinesin-8 proteins to regulate motor activity and localization.

Proper regulation of microtubules (MTs) is critical for the execution of diverse cellular processes, including mitotic spindle assembly and chromosome segregation. There are a multitude of cellular factors that regulate the dynamicity of MTs and play critical roles in mitosis. Members of the Kinesin-8 family of motor proteins act as MT-destabilizing factors to control MT length in a spatially and temporally regulated manner. In this review, we focus on recent advances in our understanding of the structure and function of the Kinesin-8 motor domain, and the emerging contributions of the C-terminal tail of Kinesin-8 proteins to regulate motor activity and localization.

Tight regulation of microtubule dynamics and microtubule organization is necessary for proper spindle assembly and chromosome segregation. The microtubule destabilizing Kinesin-8, Kif18B, controls astral microtubule dynamics and spindle positioning. Kif18B interacts with importin alpha/beta as well as with the plus-tip tracking protein EB1, but how these associations modulate Kif18B activity or function is not known. We mapped the key binding sites on Kif18B, made residue-specific mutations, and assessed their impact on Kif18B function. Blocking EB1 interaction disrupted Kif18B MT plus-end accumulation and inhibited its ability to control astral microtubule length in cells. Blocking importin alpha/beta interaction reduced Kif18B plus-end accumulation on astral MTs but did not inhibit its ability to control astral MT length. In vitro, importin alpha/beta increased Kif18B binding to the microtubule lattice, which enhanced Kif18B accumulation at microtubule plus ends, and stimulated microtubule destabilization, suggesting that the importins spatially regulate Kif18B. In contrast, EB1 promoted microtubule destabilization without increasing lattice binding in vitro, which suggests that EB1 and importin alpha/beta have distinct roles in the regulation of astral microtubule dynamics. We propose that Ran-regulation is important not only to control motor function near chromatin but also provides a spatial control mechanism to modulate microtubule binding of NLS-containing spindle assembly factors.