The molecular basis for kinesin functional specificity during mitosis

Abstract

Microtubule-based motor proteins play key roles during mitosis to assemble the bipolar spindle, define the cell division axis, and align and segregate the chromosomes. The majority of mitotic motors are members of the kinesin superfamily. Despite sharing a conserved catalytic core, each kinesin has distinct functions and localization, and is uniquely regulated in time and space. These distinct behaviors and functional specificity are generated by variations in the enzymatic domain as well as the non-conserved regions outside of the kinesin motor domain and the stalk. These flanking regions can directly modulate the properties of the kinesin motor through dimerization or self-interactions, and can associate with extrinsic factors, such as microtubule or DNA binding proteins, to provide additional functional properties. This review discusses the recently identified molecular mechanisms that explain how the control and functional specification of mitotic kinesins is achieved. © 2013 Wiley Periodicals, Inc.

Mechanisms of Mitotic Spindle Assembly

“…Kinesins walk toward MT plus ends and exist as a large superfamily with differing motor properties and cargo-binding domains (48). By contrast, only one cytoplasmic dynein fulfills the role of the minus-end-directed motor, which gets recruited by specific adapter proteins and thereby activated for transport once loaded with the right cargo (49, 50).…”

Prime movers: the mechanochemistry of mitotic kinesins

“…Understanding the ways in which spindle self-organisation and dynamics emerge from the interactions of kinesins with dynamic microtubules demands that we understand the special force-generating characteristics of each type of mitotic kinesin. For a discussion of the functional diversity contributed by the tail domains of mitotic kinesins, see 50 . We now describe kinesin subfamily specialisations in the context of specific mitotic processes.…”

Kinesin-12 Kif15 Targets Kinetochore Fibers through an Intrinsic Two-Step Mechanism

“…At the onset of mitosis, kinesins alter the organization and dynamics of MTs to catalyze spindle assembly [6]. The design principles of each mitotic kinesin appear to be optimally tuned for a specific task [7]. For example, the Kinesin-5 Eg5 tetramerizes to slide anti-parallel MTs apart [8] and thereby establish spindle bipolarity [9].…”