title: A TOG Protein Confers Tension Sensitivity to Kinetochore-Microtubule Attachments.
abstract: The development and survival of all organisms depends on equal partitioning of their genomes during cell division. Accurate chromosome segregation requires selective stabilization of kinetochore-microtubule attachments that come under tension due to opposing pulling forces exerted on sister kinetochores by dynamic microtubule tips. Here, we show that the XMAP215 family member, Stu2, makes a major contribution to kinetochore-microtubule coupling. Stu2 and its human ortholog, ch-TOG, exhibit a conserved interaction with the Ndc80 kinetochore complex that strengthens its attachment to microtubule tips. Strikingly, Stu2 can either stabilize or destabilize kinetochore attachments, depending on the level of kinetochore tension and whether the microtubule tip is assembling or disassembling. These dichotomous effects of Stu2 are independent of its previously studied regulation of microtubule dynamics. Altogether, our results demonstrate how a kinetochore-associated factor can confer opposing, tension-dependent effects to selectively stabilize tension-bearing attachments, providing mechanistic insight into the basis for accuracy during chromosome segregation.
authors.affiliation: Howard Hughes Medical Institute, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Miller
authors.affiliation: Department of Physiology & Biophysics, University of Washington, Seattle, WA 98195, USA. Electronic address: casbury@uw.edu.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Asbury
authors.affiliation: Howard Hughes Medical Institute, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Electronic address: sbiggins@fredhutch.org.
authors.forename: Sue
authors.initials: S
authors.lastname: Biggins
mesh_terms: D001696:Biomechanical Phenomena; D020090:Chromosome Segregation; D006801:Humans; D018386:Kinetochores / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D008870:Microtubules / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*
chemical_list: C454180:CKAP5 protein, human; D008869:Microtubule-Associated Proteins; C112472:NDC80 protein, S cerevisiae; D009687:Nuclear Proteins; C109414:STU2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins