Yeast kinesin-8 depolymerizes microtubules in a length-dependent manner.
The microtubule cytoskeleton and the mitotic spindle are highly dynamic structures, yet their sizes are remarkably constant, thus indicating that the growth and shrinkage of their constituent microtubules are finely balanced. This balance is achieved, in part, through kinesin-8 proteins (such as Kip3p in budding yeast and KLP67A in Drosophila) that destabilize microtubules. Here, we directly demonstrate that Kip3p destabilizes microtubules by depolymerizing them--accounting for the effects of kinesin-8 perturbations on microtubule and spindle length observed in fungi and metazoan cells. Furthermore, using single-molecule microscopy assays, we show that Kip3p has several properties that distinguish it from other depolymerizing kinesins, such as the kinesin-13 MCAK. First, Kip3p disassembles microtubules exclusively at the plus end and second, remarkably, Kip3p depolymerizes longer microtubules faster than shorter ones. These properties are consequences of Kip3p being a highly processive, plus-end-directed motor, both in vitro and in vivo. Length-dependent depolymerization provides a new mechanism for controlling the lengths of subcellular structures.
Varga
Vladimir
V
Max Planck Institute of Molecular Cell Biology & Genetics, Pfotenhauerstr. 108, 01307 Dresden, Germany.
Helenius
Jonne
J
Tanaka
Kozo
K
Hyman
Anthony A
AA
Tanaka
Tomoyuki U
TU
Howard
Jonathon
J
D000818:Animals; D016547:Kinesins / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D008870:Microtubules / Q000502:physiology*; D020409:Molecular Motor Proteins / Q000502:physiology*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D008941:Spindle Apparatus / Q000502:physiology*; D013552:Swine; D014404:Tubulin / Q000378:metabolism
C108256:KIP3 protein, S cerevisiae; D008869:Microtubule-Associated Proteins; D020409:Molecular Motor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014404:Tubulin; D016547:Kinesins