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1、TitileSummaryDuring cell division, mitotic spindles are assembled by nuciotubule-based motor piotenisl, 2. The bipolar organization of spindles is essential for proper segiegation of cliiomosomes, and requires plus-end-duected homotetrameiic motor proteins of the widely conseived kmesin-5 (BimC) fan
2、iily3 Hypotheses for bipolar spmdle fonnation include the push-pull mitotic muscle1 model, in which kinesin-5 and opposing motor proteins act between oveilapping microtubules2, 4、5. Howevei; the precise roles of kinesm-5 duiing this process are uiikiiown. Heie we show that the vertebrate kuiesm-5 Eg
3、5 drives the slidmg of microtubules depending on their relative oiientation We found in contiolled m vitro assays that Eg5 lias the lemaikable capability of sunultaneously movmg at 20 mil s-1 towards the plus-ends of each of the two microtubules it ciosslniks. For anti-parallel nuciotubules, tlus re
4、sults m relative sliding at 40 mn s-1, comparable to spindle pole sepaiation rates in vivo6. Fuitliennore, we found that Eg5 can tether miciotubule plus-ends, suggesting an additional microtubule-binding mode for Eg5 Oui results demonstrate how membefs of the kinesin-5 family axe likely to fiinction
5、 ui mitosis, pushing apart uiteipolar nuciotubules as well as lecnuting nuciotubules into bundles that are subsequently polarized by relative slidmg We anticipate oui assay to be a startmg point for more sophisticated m vitro models of mitotic spindles. For example, the uidividual and combined actio
6、n of multiple mitotic motors could be tested, including minus-end-dnected motors opposing Eg5 motility. Fuitliennore, Eg5 uilnbition is a major target of anti-cancei drug development, and a well-defined and quantitative assay foi motoi fiinction will be relevant for such developmentsContentTitile1Su
7、mmary11 Introduction11.1 Restatement of the Pi oblem11.2 Backgiound11.1.1 Conunon Solving Tecluuque11 1.2 Previous Works11.3 Example12 Analysis of the Problem12 1Outlme of the Approach12.2 Basic Assumptions22.3 Definitions and Key Terms23 Calculating and Simplify ing the Model24 The Model Results35
8、Validating the Model36 Strengths and Weaknesses361Strengths36.2Weaknesses37 Food for Thought38 Conclusion3References4Appendices4Appendix A Source Code4Appendix B41 Introduction1.1 Restatement of the Problem1.2 Background! Common Solving Technique1.1.2 Previous Works1.3 Example2 Analysis of the Problem2.1 Outline of the Approach2.2 Basic Assumptions2.3 Definitions and Key TermsUnitTable 1.SymbolMeaning3 Calculating and Simplifying the Model4 The Model Results5 Validating the Model6 Strengths and Weaknesses6.1 Strengths6.2 Weaknesses7 Food for ThoughtConclusionReferencesAppe
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