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The activities of these MAPs are carefully regulated to maintain proper microtubule dynamics during spindle assembly, with many of these proteins serving as [[Aurora kinase|Aurora]] and [[Polo-like kinase]] substrates.<ref name="H. Maiato, P Sampaio, C.E. Sunkel 2004 53–153"/> As a testament to this, proper microtubule dynamics can be recapitulated in ''Xenopus'' egg extract by the balanced activity of the stabilizing factor [[XMAP215]] and the destabilizing factor XKCM1.<ref>{{cite journal |author=R. Tournebize, A. Popov, K. Kinoshita, A.J. Ashford, et al.|title=Control of microtubule dynamics by the antagonistic activities of XMAP215 and XKCM1 in Xenopus egg extracts|journal=Nat Cell Biol|year=2000|volume=2|pages=13–19|pmid=10620801|doi=10.1038/71330}}</ref>
==Organizacija==
==Organizing the spindle apparatus==
[[File:Spindle assembly models.svg|thumb|left|Organizacija tipskog mitotskog vretena u [[životinja|životinjskim ćelijama]]
[[File:Spindle assembly models.svg|thumb|left|On the left is the conventional search-and-capture model in which microtubules emanating from microtubule organizing complexes undergo repeated growth and catastrophe until they bind and are stabilized by kinetochores. On the right is another model that describes the ability of microtubules to self-organize into a spindle-like structure due to their dynamics and the space constraints of the cell.]]
== Reference ==
{{reference}}
In a properly formed mitotic spindle, bi-oriented chromosomes are aligned along the equator of the cell with spindle microtubules oriented roughly perpendicular to the chromosomes, their plus-ends embedded in kinetochores and their minus-ends anchored at the cell poles. The precise orientation of this complex is required to ensure accurate chromosome segregation and to specify the cell division plane. However, it remains unclear how the spindle becomes organized. Two models predominate the field. In the ''search-and-capture model'', the spindle is predominantly organized by the poleward separation of microtubule organizing centers (MTOCs). Spindle microtubules emanate from MTOCs and 'seek' out kinetochores; when they bind a kinetochore they become stabilized and exert tension on the chromosomes. In an alternative ''self assembly'' model, microtubules undergo acentrosomal nucleation among the condensed chromosomes. Constrained by cellular dimensions, lateral associations with antiparallel microtubules via motor proteins, and end-on attachments to kinetochores, microtubules naturally adopt a spindle-like structure with chromosomes aligned along the cell equator. Although these may be viewed as 'alternative' models, both phenomena likely contribute to the organization of the mitotic spindle.
== Također pogledajte ==
*[[Mitoza]]
===Search-and-capture model===
*[[Mejpza]]
[[Kategorija:Citologija]]
In this model, microtubules are nucleated at microtubule organizing centers and undergo rapid growth and catastrophe to 'search' the cytoplasm for kinetochores. Once they bind a kinetochore, they are stabilized and their dynamics are reduced. The newly mono-oriented chromosome oscillates in space near the pole to which it is attached until a microtubule from the opposite pole binds the sister kinetochore. This second attachment further stabilizes kinetochore attachment to the mitotic spindle. Gradually, the bi-oriented chromosome is pulled towards the center of the cell until microtubule tension is balanced on both sides of the [[centromere]]; the congressed chromosome then oscillates at the metaphase plate until anaphase onset releases cohesion of the sister chromatids.
[[Kategorija:Citogenetika]]
In this model, microtubule organizing centers are localized to the cell poles, their separation driven by microtubule polymerization and 'sliding' of antiparallel spindle microtubules with respect to one another at the spindle midzone mediated by bipolar, plus-end-directed kinesins.<ref>{{cite journal |author=J. McIntosh, S.C. Landis|title=The distribution of spindle microtubules during mitosis in cultured human cells|journal=J Cell Biol|year=1971|volume=49|pages=468–497|doi=10.1083/jcb.49.2.468 |pmid=19866774 |issue=2 |pmc=2108320}}</ref><ref>{{cite journal |author=D.J. Sharp, K.L. McDonald, H.M. Brown, et al.|title=The bipolar kinesin, CLP61F, cross-links microtubules within interpolar microtubule bundles of Drosophila embryonic mitotic spindles|journal=J Cell Biol|year=1999|volume=144|pages=125–138|doi=10.1083/jcb.144.1.125 |pmid=9885249 |issue=1 |pmc=2148119}}</ref> Such sliding forces may not only account for spindle pole separation early in mitosis, but also spindle elongation during late anaphase.
===Self-organization of the mitotic spindle===
In contrast to the search-and-capture mechanism in which MTOCs largely dictate the organization of the mitotic spindle, this model proposes that microtubules are nucleated acentrosomally near chromosomes and spontaneously assemble into anti-parallel bundles and adopt a spindle-like structure.<ref>{{cite journal |author=M.A. Hallen, S.A. Endow|title=Anastral spindle assembly: a mathematical model|journal=Biophys J|year=2009|volume=97|pages=2191–2201 |doi=10.1016/j.bpj.2009.08.008 |pmid=19843451 |issue=8 |pmc=2764103}}</ref> Classic experiments by Rebecca Heald show that functional mitotic spindles and nuclei form around DNA-coated beads incubated in ''Xenopus'' egg extracts and that bipolar arrays of microtubules are formed in the absence of kinetochores and MTOCs.<ref>{{cite journal |author=R. Heald, R. Tournebize, et al. |title=Self-organization of microtubules into bipolar spindles around artificial chromosomes in Xenopus egg extracts|journal=Nature|year=1996|volume=382|pages=420–425 |doi=10.1038/382420a0 |pmid=8684481 |issue=6590}}</ref> Indeed, it has also been shown that laser ablation of centrosomes in vertebrate cells inhibits neither spindle assembly nor chromosome segregation.<ref>{{cite journal |author=A. Khodjakov, R.W. Cole, B.R. Oakley, C.L. Rieder|title=Centrosome-independent mitotic spindle formation in vertebrates|journal=Curr Biol|year=2000|volume=10|pages=59–67 |doi=10.1016/S0960-9822(99)00276-6 |pmid=10662665 |issue=2}}</ref> Under this scheme, the shape and size of the mitotic spindle are a function of the biophysical properties of the cross-linking motor proteins.<ref>{{cite journal |author=K.S. Burbank, T.J. Mitchison, D.S. Fisher|title=Slide-and-cluster models for spindle assembly|journal=Curr Biol|year=2007|volume=17|pages=1373–1383 |doi=10.1016/j.cub.2007.07.058 |pmid=17702580 |issue=16}}</ref>
==Regulation of spindle assembly==
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