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CLASPs stabilize the pre-catastrophe intermediate state between microtubule growth and shrinkage
The Journal of Cell Biology Pub Date : 2023-05-15 , DOI: 10.1083/jcb.202107027 Elizabeth J Lawrence 1 , Saptarshi Chatterjee 1 , Marija Zanic 1, 2, 3
The Journal of Cell Biology Pub Date : 2023-05-15 , DOI: 10.1083/jcb.202107027 Elizabeth J Lawrence 1 , Saptarshi Chatterjee 1 , Marija Zanic 1, 2, 3
Affiliation
Cytoplasmic linker-associated proteins (CLASPs) regulate microtubules in fundamental cellular processes. CLASPs stabilize dynamic microtubules by suppressing microtubule catastrophe and promoting rescue, the switch-like transitions between growth and shrinkage. How CLASPs specifically modulate microtubule transitions is not understood. Here, we investigate the effects of CLASPs on the pre-catastrophe intermediate state of microtubule dynamics, employing distinct microtubule substrates to mimic the intermediate state. Surprisingly, we find that CLASP1 promotes the depolymerization of stabilized microtubules in the presence of GTP, but not in the absence of nucleotide. This activity is also observed for CLASP2 family members and a minimal TOG2-domain construct. Conversely, we find that CLASP1 stabilizes unstable microtubules upon tubulin dilution in the presence of GTP. Strikingly, our results reveal that CLASP1 drives microtubule substrates with vastly different inherent stabilities into the same slowly depolymerizing state in a nucleotide-dependent manner. We interpret this state as the pre-catastrophe intermediate state. Therefore, we conclude that CLASPs suppress microtubule catastrophe by stabilizing the intermediate state between growth and shrinkage.
中文翻译:
CLASP 稳定微管生长和收缩之间的灾难前中间状态
细胞质接头相关蛋白 (CLASP) 在基本细胞过程中调节微管。CLASP 通过抑制微管灾难和促进救援(生长和收缩之间的开关式转变)来稳定动态微管。CLASP 如何特异性调节微管转变尚不清楚。在这里,我们研究了 CLASP 对微管动力学灾难前中间状态的影响,采用不同的微管基质来模拟中间状态。令人惊讶的是,我们发现 CLASP1 在 GTP 存在的情况下促进稳定微管的解聚,但在不存在核苷酸的情况下则不会。在 CLASP2 家族成员和最小 TOG2 结构域构建体中也观察到了这种活性。相反,我们发现 CLASP1 在 GTP 存在的情况下在微管蛋白稀释时稳定不稳定的微管。引人注目的是,我们的结果表明,CLASP1 以核苷酸依赖性方式驱动具有截然不同的固有稳定性的微管底物进入相同的缓慢解聚状态。我们将此状态解释为灾难前的中间状态。因此,我们得出结论,CLASP 通过稳定生长和收缩之间的中间状态来抑制微管灾难。
更新日期:2023-05-15
中文翻译:
CLASP 稳定微管生长和收缩之间的灾难前中间状态
细胞质接头相关蛋白 (CLASP) 在基本细胞过程中调节微管。CLASP 通过抑制微管灾难和促进救援(生长和收缩之间的开关式转变)来稳定动态微管。CLASP 如何特异性调节微管转变尚不清楚。在这里,我们研究了 CLASP 对微管动力学灾难前中间状态的影响,采用不同的微管基质来模拟中间状态。令人惊讶的是,我们发现 CLASP1 在 GTP 存在的情况下促进稳定微管的解聚,但在不存在核苷酸的情况下则不会。在 CLASP2 家族成员和最小 TOG2 结构域构建体中也观察到了这种活性。相反,我们发现 CLASP1 在 GTP 存在的情况下在微管蛋白稀释时稳定不稳定的微管。引人注目的是,我们的结果表明,CLASP1 以核苷酸依赖性方式驱动具有截然不同的固有稳定性的微管底物进入相同的缓慢解聚状态。我们将此状态解释为灾难前的中间状态。因此,我们得出结论,CLASP 通过稳定生长和收缩之间的中间状态来抑制微管灾难。