During mitosis, sister chromatids congress to the spindle equator and are subsequently segregated via attachment to dynamic kinetochore microtubule (kMT) plus ends. A major question is how kMT plus-end assembly is spatially regulated to achieve chromosome congression. Here we find in budding yeast that the widely conserved kinesin-5 sliding motor proteins, Cin8p and Kip1p, mediate chromosome congression by suppressing kMT plus-end assembly of longer kMTs. Of the two, Cin8p is the major effector and its activity requires a functional motor domain. In contrast, the depolymerizing kinesin-8 motor Kip3p plays a minor role in spatial regulation of yeast kMT assembly. Our analysis identified a model where kinesin-5 motors bind to kMTs, move to kMT plus ends, and upon arrival at a growing plus end promote net kMT plus-end disassembly. In conclusion, we find that length-dependent control of net kMT assembly by kinesin-5 motors yields a simple and stable self-organizing mechanism for chromosome congression.
Bibliographical noteFunding Information:
The authors thank Dominique Seetapun for providing matlab kymograph code, Drs. Tom Hays and Leah Gheber for helpful discussions, Dr. Jeff Molk for comments on the manuscript, and Marybeth Anderson for assistance with bim1Δ images. Plasmids and strains were kindly provided by Drs. S. Reed, B. Errede, M.A. Hoyt, L. Gheber, and D. Pellman. This work was supported by NIH grant GM071522 to D.J.O. K.B. is supported by NIH grant GM32238 and M.K.G. is supported by NIH NRSA grant EB005568. E.T.O. is supported in part by grant RR-00592 from the National Center for Research Resources of the NIH to A. Hoenger. L.V.P. is supported by a SPIRE fellowship (GM00678).
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