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RISS 인기검색어
- 검색키워드
- 저자 : Sturgill, Emma G. (검색결과 3 건)
- 무료
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Kinesin-12 Kif15 Targets Kinetochore Fibers through an Intrinsic Two-Step Mechanism
Sturgill, Emma G.,Das, D.,Takizawa, Y.,Shin, Y.,Collier, Scott E.,Ohi, Melanie D.,Hwang, W.,Lang, Matthew J.,Ohi, R. Current Biology Ltd ; Elsevier Science Ltd 2014 Current biology Vol.24 No.19
Proteins that recognize and act on specific subsets of microtubules (MTs) enable the varied functions of the MT cytoskeleton. We recently discovered that Kif15 localizes exclusively to kinetochore fibers (K-fibers) [1, 2] or bundles of kinetochore-MTs within the mitotic spindle. It is currently speculated that the MT-associated protein TPX2 loads Kif15 onto spindle MTs [3-5], but this model has not been rigorously tested. Here, we show that Kif15 accumulates on MT bundles as a consequence of two inherent biochemical properties. First, Kif15 is self-repressed by its C terminus. Second, Kif15 harbors a nonmotor MT-binding site, enabling dimeric Kif15 to crosslink and slide MTs. Two-MT binding activates Kif15, resulting in its accumulation on and motility within MT bundles but not on individual MTs. We propose that Kif15 targets K-fibers via an intrinsic two-step mechanism involving molecular unfolding and two-MT binding. This work challenges the current model of Kif15 regulation and provides the first account of a kinesin that specifically recognizes a higher-order MT array.
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Collective Force Regulation in Anti-parallel Microtubule Gliding by Dimeric Kif15 Kinesin Motors
Reinemann, Dana N.,Sturgill, Emma G.,Das, Dibyendu Kumar,Degen, Miriam Steiner,Vö,rö,s, Zsuzsanna,Hwang, Wonmuk,Ohi, Ryoma,Lang, Matthew J. Elsevier 2017 Current biology Vol.27 No.18
<P><B>Summary</B></P> <P>During cell division, the mitotic kinesin-5 Eg5 generates most of the force required to separate centrosomes during spindle assembly. However, Kif15, another mitotic kinesin, can replace Eg5 function, permitting mammalian cells to acquire resistance to Eg5 poisons. Unlike Eg5, the mechanism by which Kif15 generates centrosome separation forces is unknown. Here we investigated the mechanical properties and force generation capacity of Kif15 at the single-molecule level using optical tweezers. We found that the non-motor microtubule-binding tail domain interacts with the microtubule’s E-hook tail with a rupture force higher than the stall force of the motor. This allows Kif15 dimers to productively and efficiently generate forces that could potentially slide microtubules apart. Using an in vitro optical trapping and fluorescence assay, we found that Kif15 slides anti-parallel microtubules apart with gradual force buildup while parallel microtubule bundles remain stationary with a small amount of antagonizing force generated. A stochastic simulation shows the essential role of Kif15’s tail domain for load storage within the Kif15-microtubule system. These results suggest a mechanism for how Kif15 rescues bipolar spindle assembly.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Kif15 transports microtubules in bundles through motor and non-motor coordination </LI> <LI> Kif15’s non-motor microtubule-binding site (Coil-1) is stronger than stall force </LI> <LI> Kif15 generates force in anti-parallel bundles and has a force-feedback mechanism </LI> <LI> Coil-1 tethering is needed for the force ramp and plateau in anti-parallel bundles </LI> </UL> </P>
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Invited Article : State of the Science: Salivary Biomarker Utilization for Stress Research
( An Kyungeh ),( Starkweather Angela ),( Sturgill Jamie L ),( Kao Hsueh Fen S ),( Salyer Jeanne ) 서울대학교 간호과학연구소 2014 간호학의 지평 Vol.11 No.2
Purpose: The use of salivary biomarkers for stress research is increasing based on the convenience of collection, affordability and scientific merit. This short review provides an overview of the state of the science of salivary biomarkers utilized in research related to stress. Methods: An integrative review was conducted. Results: The trend of utilizing salivary biomarkers in stress research was reviewed, specifically, focusing on the use of endocrine and inflammatory biomarkers incorporated in previous stress research. Then, a review of sampling procedures for salivary biomarkers and the analytic methods is provided. Finally, a discussion on the strengths and areas for improvement in the use of salivary biomarkers in stress research is included. Conclusion: Salivary biomarkers as an alternative to blood biomarkers are increasingly being recognized as a legitimate source for analyzing the stress response in humans.
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