Mechanisms of Astral Microtubule Regulation by Kinesin Motor Proteins

Abstract

During mitotic division cells construct a bipolar spindle that aligns and accurately divides the chromosomes. Correct construction and positioning of the spindle is important to prevent segregation errors. Astral microtubules connect the spindle poles to the cell cortex and provide the pushing and pulling forces required to accurately position the spindle in the cell. Two kinesin motor proteins, Kif18b (Kinesin-8) and MCAK (Kinesin-13), are important regulators of astral microtubule length and spindle positioning in human cells. We are investigating the mechanism by which Kif18b regulates microtubule length both in vitro and in cells. We have found that Kif18b is a highly processive motor that targets microtubule plus ends and alters their dynamic behaviour. Kif18b is regulated through its C-terminal tail region and this is important for targeting to astral microtubule plus tips. Although Kif18b motor domains are capable of depolymerising stable microtubules its tail domain counteracts this ability. We present new data exploring the interaction between Kif18b and microtubule plus tip proteins and propose a model for Kif18b mediated astral microtubule regulation.