Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY, USA.
Cell Cycle. 2010 Jun 15;9(12):2403-11. doi: 10.4161/cc.9.12.11916.
Katanin is a microtubule severing enzyme with demonstrated roles in a variety of cellular activities including mitosis. Here we identify the closely related, but relatively uncharacterized human protein, Katanin-like 1 (KL1), as a novel mitotic regulator. Over expression of KL1 in tissue culture cells results in the complete disassembly of cellular microtubules strongly suggesting that it is an active microtubule severing protein. During mitosis, the localization of KL1 is restricted to spindle poles and is notably absent from centrosomes. This is in clear contrast to conventional Katanin whose localization extends from centrosomes onto poles. Consistent with its localization, siRNA depletion of KL1 from U2OS cells results in a specific and significant reduction in the density of microtubules at spindle poles and significantly increases spindle length. Depletion of KL1 also alters the distribution of gamma-tubulin at centrosomes/spindle poles. Despite its impact on spindle morphology, we could find no evidence that KL1 influences anaphase chromosome motility. Based on our findings, we propose that KL1-mediated microtubule severing is utilized to generate microtubule seeds within the poles and that loss of this activity alters the normal balance of motor-generated forces that determine spindle length.
katanin 是一种微管切割酶，已被证明在多种细胞活动中发挥作用，包括有丝分裂。在这里，我们将密切相关但相对未被充分描述的人类蛋白 katanin-like 1（kl1）鉴定为一种新的有丝分裂调节因子。kl1 在组织培养细胞中的过表达导致细胞微管的完全解体，强烈表明它是一种活性微管切割蛋白。在有丝分裂过程中，kl1 的定位局限于纺锤体极，明显不存在于中心体。这与传统的katanin 形成鲜明对比，后者的定位从中心体延伸到极。与其定位一致，kl1 的 siRNA 耗尽导致纺锤体极处微管的密度显著降低，纺锤体长度显著增加。kl1 的耗竭也改变了中心体/纺锤体极处的γ-微管蛋白的分布。尽管它对纺锤体形态有影响，但我们没有发现 kl1 影响后期染色体运动的证据。基于我们的发现，我们提出 kl1 介导的微管切割用于在极内生成微管种子，并且这种活性的丧失改变了决定纺锤体长度的马达产生力的正常平衡。
