kinesin13

Kinesin-13 refers to a subfamily of the kinesin superfamily of motor proteins that function primarily as microtubule depolymerizers rather than conventional plus-end–directed motors. In humans, the best characterized members are KIF2A, KIF2B, and KIF2C (the latter commonly known as mitotic centromere-associated kinesin, MCAK). Orthologs exist in many eukaryotes, including XKCM1 in Xenopus. Kinesin-13 proteins are nonprocessive and do not move along microtubules; instead they localize to microtubule ends and catalyze removal of tubulin subunits, promoting depolymerization in an ATP-dependent manner. The motor domain is conserved, but the neck and tail regions diverge from motile kinesins, enabling end-binding and end-destabilizing activity.

Functionally, kinesin-13 proteins regulate microtubule dynamics in multiple contexts. During mitosis they control spindle length, chromosome alignment at kinetochores, and spindle pole integrity by depolymerizing kinetochore and interpolar microtubules. In interphase cells they regulate non-centrosomal microtubule dynamics, and in neurons they influence neurite outgrowth and dendritic architecture through localized depolymerization.

Regulation occurs through phosphorylation by mitotic kinases such as Aurora B and Aurora A, interactions with microtubule plus-end tracking factors like EB proteins, and autoregulatory intramolecular interactions. These controls determine localization, activity, and affinity for microtubule ends.

Clinical and functional significance: Altered expression or activity of kinesin-13 family members is associated with chromosomal instability in cancer and with developmental processes in organisms. Because of their distinctive end-depolymerizing mechanism, kinesin-13 proteins are studied as potential targets for therapeutic intervention and as fundamental regulators of cellular microtubule dynamics.