The Kinesin-13 family was originally discovered to possess the startling capability to depolymerize microtubules rather than translocate along their surface, as is more common with kinesins. Previously, they have been called M-type or Kin I kinesins to describe the property that the motor domain is located in the middle of the amino acid sequence of the protein (Internal rather than N-terminal or C-terminal). This family possesses the unusual property of preferential and tight association with microtubule ends as compared to the surface lattice. The microtubule-binding surface of the core motor is convex and stabilizes the curved microtubule protofilament structure seen at the ends of depolymerizing microtubules. In agreement with kinetic and structural studies, the Kinesin-13 family of kinesins promotes catastrophe and increases the intrinsic dynamicity of live microtubules in cells and in vitro (Walczak, 2003).
Drosophila, the mouse and humans possess three unique Kinesin-13 family genes. Pairwise comparisons of full-length protein and motor domain sequences identify putative orthologues as DmKlp10A/MmKif2A/HsKin2 (HsKif2); DmKlp59C/MmKif2C/HsMCAK; and DmKlp59D/MmKif2B/HsKlp17 (C.D. Yankel & S.A. Endow, 2006). Presently, the best studied are the mitotic Kinesin-13 proteins. Studies in both D. melanogaster and human cells suggest a division of labor between Kinesin-13 family members, such that different proteins contribute microtubule depolymerizing activity to the centrosome [DmKlp10A/MmKif2A/HsKin2 (HsKif2)] and centromere [DmKlp59C/MmKif2C/HsMCAK] during mitosis. These activities have been shown to be essential for spindle morphogenesis and chromosome segregation. Analogies with the powerful yeast mitotic system are difficult because the Kinesin-13 family has no apparent members represented in the S. cerevisiae genome. Instead, a sole member of a related family, Kip3, is present. There may be either functional overlap or interdependence between the Kinesin-13 and the Kinesin-8 (Kip-3) families (Moore and Wordeman, 2004). The Kinesin-13 family member, HsMCAK/MmKIF2C, is negatively regulated by the Aurora B kinase during mitosis and positively regulated by the inner centromere protein ICIS (Gorbsky, 2004). Regulation of microtubule-dependent activity by kinases and other effectors is likely to become a recurrent theme for the Kinesin-13 family and other kinesins.
Tissue-specific splice variants have been identified for HsMCAK/MmKIF2C in testis and also for MmKIF2A. An isoform of MmKIF2A (MmKIF2Aα) is enriched in neural tissue. A mouse knockout of MmKIF2Aα resulted in unusually long collateral branches, culminating in defects in neuronal migration and lethal abnormalities in the wiring of the brain. Thus, in addition to cell division, the microtubule depolymerizing activity of Kinesin-13 family members is required for patterning the connections in the brain (Moore & Wordeman, 2004).
Contributed by Linda Wordeman
Recent Reviews
Gorbsky, G.J. 2004
- Mitosis: MCAK under the aura of Aurora B. Curr Biol. 14:R346-8.
- The mechanism, function and regulation of depolymerizing kinesins during mitosis. Trends Cell Biol. 14:537-46.
- The Kin I kinesins are microtubule end-stimulated ATPases. Mol Cell. 11:286-8.
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