Keyes Brice E, Burke Daniel J
Department of Biochemistry and Molecular Genetics, University of Virginia Medical Center, Charlottesville, VA 22908, USA.
Curr Biol. 2009 Mar 24;19(6):472-8. doi: 10.1016/j.cub.2009.01.068. Epub 2009 Mar 12.
Microtubules are polymers composed of alpha-beta tubulin heterodimers that assemble into microtubules. Microtubules are dynamic structures that have periods of both growth and shrinkage by addition and removal of subunits from the polymer. Microtubules stochastically switch between periods of growth and shrinkage, termed dynamic instability. Dynamic instability is coupled to the GTPase activity of the beta-tubulin subunit of the tubulin heterodimer. Microtubule dynamics are regulated by microtubule-associated proteins (MAPs) that interact with microtubules to regulate dynamic instability. MAPs in budding yeast have been identified that bind microtubule ends (Bim1), that stabilize microtubule structures (Stu2), that bundle microtubules by forming cross-bridges (Ase1), and that interact with microtubules at the kinetochore (Cin8, Kar3, Kip3). IRC15 was previously identified in four different genetic screens for mutants affecting chromosome transmission or repair [11-14]. Here we present evidence that Irc15 is a microtubule-associated protein, localizing to microtubules in vivo and binding to purified microtubules in vitro. Irc15 regulates microtubule dynamics in vivo and loss of IRC15 function leads to delayed mitotic progression, resulting from failure to establish tension between sister kinetochores.
微管是由α-β微管蛋白异二聚体组成的聚合物，这些异二聚体组装成微管。微管是动态结构，通过聚合物中亚基的添加和去除，会经历生长和收缩阶段。微管在生长和收缩阶段之间随机切换，这被称为动态不稳定性。动态不稳定性与微管蛋白异二聚体的β-微管蛋白亚基的GTPase活性相关联。微管动力学受微管相关蛋白（MAPs）调节，这些蛋白与微管相互作用以调节动态不稳定性。已在芽殖酵母中鉴定出多种MAPs，它们分别结合微管末端（Bim1）、稳定微管结构（Stu2）、通过形成交叉桥来捆绑微管（Ase1）以及在动粒处与微管相互作用（Cin8、Kar3、Kip3）。IRC15先前在四个不同的遗传筛选中被鉴定出来，这些筛选针对影响染色体传递或修复的突变体[11 - 14]。在此我们提供证据表明Irc15是一种微管相关蛋白，在体内定位于微管，并在体外与纯化的微管结合。Irc15在体内调节微管动力学，并且IRC15功能的丧失会导致有丝分裂进程延迟，这是由于未能在姐妹动粒之间建立张力所致。
