目前，關(guān)于細(xì)胞分裂各時期的研究并未充分的展開,。細(xì)胞分裂產(chǎn)生的錯誤可能引起突變,，進(jìn)而導(dǎo)致癌癥的發(fā)生，此類研究有助于探究在不可控的細(xì)胞復(fù)制中染色體的異常情況,。
細(xì)胞分裂主要分為四個期,，其中分裂后期指染色體分開并移向兩極的時期，當(dāng)子染色體到達(dá)兩極后,，標(biāo)志這一時期結(jié)束,。這個階段,，容易產(chǎn)生錯誤，比如說損壞和分配不均,，從而導(dǎo)致細(xì)胞的癌變,。分裂后期又分為A、B兩個階段,。后期A,，與染色體結(jié)合的微管蛋白牽引染色體向兩極的中心體移動；后期B,，指兩極間距離拉大的過程,。后期A已經(jīng)被廣泛的研究。而關(guān)于后期B的研究并不多,。
在2009年8月14日《發(fā)育細(xì)胞》雜志上,，一支跨國多學(xué)科合作團(tuán)隊(duì)發(fā)現(xiàn)一種新的分子機(jī)制。該機(jī)制是在細(xì)胞分裂后期B期發(fā)現(xiàn)的,。該團(tuán)隊(duì)通過在酵母系統(tǒng)中開展了對分子馬達(dá)進(jìn)行突變的研究,，并且對其每一個突變的細(xì)胞分裂時間進(jìn)行了測定?？茖W(xué)家們報道了被稱為Klp9p的分子馬達(dá)和被綁定于紡錘中央?yún)^(qū)Ase1p微管結(jié)合蛋白相互作用過程,。研究發(fā)現(xiàn)細(xì)胞分裂后期B期，Klp9p突變的細(xì)胞分裂明顯減緩,。當(dāng)Klp9p和Ase1p協(xié)作才能發(fā)揮正常的作用和功能,。更重要的是Klp9p-Ase1p復(fù)合物能夠被Cdc2p蛋白磷酸化從而阻斷。但是,，蛋白Clp1p可以對Klp9p和Ase1p去磷酸化,，從而解除阻斷，使兩種蛋白重新形成化合物使細(xì)胞分裂繼續(xù),。
之前關(guān)于紡錘體中央?yún)^(qū)域的描述,，并沒有通過分子馬達(dá)、微管結(jié)合蛋白和借助磷酸鹽開關(guān)綁定和調(diào)控該區(qū)域的方式來提及,。Tran團(tuán)隊(duì)就細(xì)胞分裂后期B給出了一個完美的分子結(jié)構(gòu)描述,，證明了Klp9p,Ase1p, Cdc2p和Clp1p-每一個蛋白在細(xì)胞分裂后期B期中的扮演的重要角色。
據(jù)Tran所言,，該發(fā)現(xiàn)對于癌癥研究具有潛在的重要影響,。不恰當(dāng)?shù)娜旧w分離能導(dǎo)致異倍染色體的出現(xiàn)，而這恰好是許多癌癥的特征,。(生物谷Bioon.com)
生物谷推薦原始出處：
Developmental Cell, Volume 17, Issue 2, 257-267, 18 August 2009. doi:10.1016/j.devcel.2009.06.012
Phospho-Regulated Interaction between Kinesin-6 Klp9p and Microtubule Bundler Ase1p Promotes Spindle Elongation
Chuanhai Fu 1,Jonathan J. Ward 2,Isabelle Loiodice 1,3,Guilhem Velve-Casquillas 1,3, Francois J. Nedelec 2,*, and Phong T. Tran 1,3,*
1 Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 10104, USA
2 Cell Biology and Biophysics Program, EMBL, Heidelberg 69117, Germany
3 Institut Curie, CNRS UMR144, Paris 75005, France
* Corresponding author
Summary
The spindle midzone composed of antiparallel microtubules, microtubule-associated proteins (MAPs), and motors is the structure responsible for microtubule organization and sliding during anaphase B. In general, MAPs and motors stabilize the midzone and motors produce sliding. We show that fission yeast kinesin-6 motor klp9p binds to the microtubule antiparallel bundler ase1p at the midzone at anaphase B onset. This interaction depends upon the phosphorylation states of klp9p and ase1p. The cyclin-dependent kinase cdc2p phosphorylates and its antagonist phosphatase clp1p dephosphorylates klp9p and ase1p to control the position and timing of klp9p-ase1p interaction. Failure of klp9p-ase1p binding leads to decreased spindle elongation velocity. The ase1p-mediated recruitment of klp9p to the midzone accelerates pole separation, as suggested by computer simulation. Our findings indicate that a phosphorylation switch controls the spatial-temporal interactions of motors and MAPs for proper anaphase B, and suggest a mechanism whereby a specific motor-MAP conformation enables efficient microtubule sliding.
