How kinesin motor proteins drive mitotic spindle function: Lessons from molecular assays

Abstract

Kinesins are enzymes that use the energy of ATP to perform mechanical work. There are approximately 14 families of kinesins within the kinesin superfamily. Family classification is derived primarily from alignments of the sequences of the core motor domain. For this reason, the enzymatic behavior and motility of each motor generally reflects its family. At the cellular level, kinesin motors perform a variety of functions during cell division and within the mitotic spindle to ensure that chromosomes are segregated with the highest fidelity possible. The cellular functions of these motors are intimately related to their mechanical and enzymatic properties at the single molecule level. For this reason, motility studies designed to evaluate the activity of purified molecular motors are a requirement in order to understand, mechanistically, how these motors make the mitotic spindle work and what can cause the spindle to fail. This review will focus on a selection of illustrative kinesins, which have been studied at the molecular level in order to inform our understanding of their function in cells. In addition, the review will endeavor to point out some kinesins that have been studied extensively but which still lack sufficient molecular underpinnings to fully predict their contribution to spindle function.

Figure 1

Chromosome segregation in the Lillium pollen shore mother cell from Mottier (1903)(4).

Figure 2

Motors contribute diverse mechanical activities to the mitotic spindle. Minus-end directed motility (examples are NCD and dynein), plus-end directed motility (Kid, MKLP1, MKLP2, and others); bipolar plus-end directed motility (Eg5, presently no bipolar minus-end directed motors have been reported); plus- and minus-end directed motility transporting signaling molecules (MKLP1, dynein); depolymerizing and end modulating activity (MCAK, Kif18A, Xklp1, Nod). Motors may couple to microtubules (left inset), spindle matrix components such as NuMa(140, 141) (right inset) or other cargo.