Fong Kimberly K, Sarangapani Krishna K, Yusko Erik C, Riffle Michael, Llauró Aida, Graczyk Beth, Davis Trisha N, Asbury Charles L
Department of Biochemistry, University of Washington, Seattle, WA 98195.
Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195.
Mol Biol Cell. 2017 Jul 7;28(14):1853-1861. doi: 10.1091/mbc.E17-01-0034. Epub 2017 Mar 22.
Centrosomes, or spindle pole bodies (SPBs) in yeast, are vital mechanical hubs that maintain load-bearing attachments to microtubules during mitotic spindle assembly, spindle positioning, and chromosome segregation. However, the strength of microtubule-centrosome attachments is unknown, and the possibility that mechanical force might regulate centrosome function has scarcely been explored. To uncover how centrosomes sustain and regulate force, we purified SPBs from budding yeast and used laser trapping to manipulate single attached microtubules in vitro. Our experiments reveal that SPB-microtubule attachments are extraordinarily strong, rupturing at forces approximately fourfold higher than kinetochore attachments under identical loading conditions. Furthermore, removal of the calmodulin-binding site from the SPB component Spc110 weakens SPB-microtubule attachment in vitro and sensitizes cells to increased SPB stress in vivo. These observations show that calmodulin binding contributes to SPB mechanical integrity and suggest that its removal may cause pole delamination and mitotic failure when spindle forces are elevated. We propose that the very high strength of SPB-microtubule attachments may be important for spindle integrity in mitotic cells so that tensile forces generated at kinetochores do not cause microtubule detachment and delamination at SPBs.
中心体,即酵母中的纺锤体极体(SPB),是至关重要的机械枢纽,在有丝分裂纺锤体组装、纺锤体定位和染色体分离过程中维持与微管的承重连接。然而,微管与中心体连接的强度尚不清楚,而且机械力可能调节中心体功能这一可能性几乎未被探索。为了揭示中心体如何承受和调节力,我们从出芽酵母中纯化了SPB,并在体外使用激光捕获技术操纵单个附着的微管。我们的实验表明,SPB与微管的连接异常牢固,在相同加载条件下,其断裂力比动粒连接高出约四倍。此外,从SPB组分Spc110上去除钙调蛋白结合位点会削弱体外SPB与微管的连接,并使细胞在体内对增加的SPB应激敏感。这些观察结果表明钙调蛋白结合有助于SPB的机械完整性,并表明当纺锤体力升高时,去除钙调蛋白可能导致极体分层和有丝分裂失败。我们提出,SPB与微管连接的极高强度可能对有丝分裂细胞中纺锤体的完整性很重要,这样动粒产生的拉力就不会导致微管在SPB处脱离和分层。