Article

In search of an optimal ring to couple microtubule depolymerization to processive chromosome motions

Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309-0347, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 12/2007; 104(48):19017-22. DOI: 10.1073/pnas.0709524104
Source: PubMed

ABSTRACT Mitotic chromosome motions are driven by microtubules (MTs) and associated proteins that couple kinetochores to MT ends. A good coupler should ensure a high stability of attachment, even when the chromosome changes direction or experiences a large opposing force. The optimal coupler is also expected to be efficient in converting the energy of MT depolymerization into chromosome motility. As was shown years ago, a "sleeve"-based, chromosome-associated structure could, in principle, couple MT dynamics to chromosome motion. A recently identified kinetochore complex from yeast, the "Dam1" or "DASH" complex, may function as an encircling coupler in vivo. Some features of the Dam1 ring differ from those of the "sleeve," but whether these differences are significant has not been examined. Here, we analyze theoretically the biomechanical properties of encircling couplers that have properties of the Dam1/DASH complex, such as its large diameter and inward-directed extensions. We demonstrate that, if the coupler is modeled as a wide ring with links that bind the MT wall, its optimal performance is achieved when the linkers are flexible and their binding to tubulin dimers is strong. The diffusive movement of such a coupler is limited, but MT depolymerization can drive its motion via a "forced walk," whose features differ significantly from those of the mechanisms based on biased diffusion. Our analysis identifies key experimental parameters whose values should determine whether the Dam1/DASH ring moves via diffusion or a forced walk.

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Available from: Ekaterina L Grishchuk, Aug 28, 2015
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    • "omplexes from budding yeast have also been shown to synergize in forming load - bearing attachments to depolymerizing microtubules ( Lampert et al . , 2010 ; Tien et al . , 2010 ) . The models previously described for the Ndc80 and Dam1 complexes were under the implicit assumption that each complex interacts with the straight microtubule lattice ( Efremov et al . , 2007 ; Hill , 1985 ) . Here , we demonstrated that the human Ska1 complex autonomously tracks with depolymerizing micro - tubules . We propose that the Ska1 complex remains associ - ated with depolymerizing microtubules by not only associating with and diffusing along the straight microtubule lattice , but also by interacting with the curved"
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    • "The discovery that DASH forms rings around microtubules captured the imagination of researchers interested in the microtubule-kinetochore interface (Salmon 2005). Rings provide an excellent model for a microtubule plus end tracker that could couple depolymerisation to movement (Efremov et al. 2007; Armond and Turner 2010). A ringbased coupler bound weakly to the plus end would effectively track the depolymerising tip as the splayed microtubule end would push on the ring as the microtubule depolymerises (Fig. 1a). "
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    • "We were, therefore, able to produce an accurate snapshot of Dam1 ring–microtubule orientations. The distribution of angles we see here would come, according to the modeling of Ataullakhanov and colleagues (Efremov et al., 2007), from two binding sites on the microtubule wall. However, we would also expect to see a similar distribution from Dam1–microtubule binding involving flexible elements, for example, interactions between the E-hook of tubulin and extended elements from the Dam1 complex. "
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