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Molecule Motors Control Length Of Antiparallel Microtubule Overlaps

Posted on:2013-06-11Degree:MasterType:Thesis
Country:ChinaCandidate:C H ZhangFull Text:PDF
GTID:2230330374468210Subject:Biophysics
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The spindle dynamic is important to mitosis in cells, it is vital in chromosomesegregation, cytokinesis and function as cleavage interface to fulfill the formation of subcells.The spindle is mainly made by microtubules to sustain the spindle structure. Its dynamicexpansion is controlled by the microtubule assembly and disassembly according to theinteraction between molecular motors and a series of complex supramolecular structures andmicrotubules. From lots of research we can discover that at anaphase B in vivo, there forms astable antiparrallel microtubule bundles (about2~3μm in length) in spindle midzone to sustainstable cell and following process. From experiments in vitro, we notice that PRC1canautonomously recognize antiparallel microtubule overlap, and selectively recruit awful lots ofXklp1at the overlap region to inhibit the growth and shrinkage of tubulin to maintain a stablemicrotubule overlap length. But it is not understood on how Xklp1inhibit the growth andshrinkage of microtubule, so this paperis trying to find out the specific inhibition mechanismof antiparallel microtubule overlaps by molecular motor Xklp1according to the simulation ofantiparallel microtubule overlap growth.Based on two model assumptions, we use Monte Carlo numerical simulation method tostudy the regulation mechanism of antiparallel microtubule overlaps by molecular motorXklp1in the presence of PRC1in this paper. The one is that Xklp1’s inhibitory efect is due toa direct prevention of loss or gain of tubulin dimmers at the plus end of microtubule, which iscalled capping model; and the other one is that all the Xklp1which bound to the microtubulescould induce global structural changes in the microtubule which influence the microtubuleends, causing inhibition of microtubule dynamics, which is called allosteric inhibition model.It found that the result obtained from the capping model is in agreement with experimentsqualitatively, the overlap length is decreased with increasing Xklp1concentration, while theconcentration of Xklp1is lower than a threshold value, and the antiparallel microtubule overlap growspersistently, which make it cannot reach a steady-state length, but the results are far from experimentsin quantity, even by adjusting the values ofk band can not make the final results agreewell with the experimental ones; while the result obtained from the allosteric inhibition model is in good agreement with experiment’s both in quality and in quantity. So the regulatingmechanism of microtubule growth and shrinkage by molecular motors is more likely the latter,induced by microtubule conformational changes caused by motors combined on themicrotubules, rather than the consequence of directed inhibition of motors.This allosteric inhibition model can also explain some other experimental phenomena,such as single microtubule growth with the increasing motor concentration, and the totallyinhibition of microtubule growth and shrinkage.This research can help us understand the inhibition mechanism of microtubule dynamicsby Xklp1and the regulatory mechanism of steady-state midzone in mitotic anaphase. Sincethe models are simple, the action mechanism of Xklp1to microtubule needs to be checked byfurther experiments.
Keywords/Search Tags:Monte-Carlo simulation, antiparallel microtubule overlaps, motor, microtubule dynamics
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