School of Biological Sciences, College of Science, Nanyang Technological University, 60 Nanyang Drive, 637551, Singapore.
School of Biological Sciences, College of Science, Nanyang Technological University, 60 Nanyang Drive, 637551, Singapore
Open Biol. 2018 Jun;8(6). doi: 10.1098/rsob.170202.
Abnormal centrosome number and function have been implicated in tumour development. LIM kinase1 (LIMK1), a regulator of actin cytoskeleton dynamics, is found to localize at the mitotic centrosome. However, its role at the centrosome is not fully explored. Here, we report that LIMK1 depletion resulted in multi-polar spindles and defocusing of centrosomes, implicating its involvement in the regulation of mitotic centrosome integrity. LIMK1 could influence centrosome integrity by modulating centrosomal protein localization at the spindle pole. Interestingly, dynein light intermediate chains (LICs) are able to rescue the defects observed in LIMK1-depleted cells. We found that LICs are potential novel interacting partners and substrates of LIMK1 and that LIMK1 phosphorylation regulates cytoplasmic dynein function in centrosomal protein transport, which in turn impacts mitotic spindle pole integrity.
异常的中心体数量和功能与肿瘤的发生发展有关。LIM 激酶 1（LIMK1）是细胞骨架动力学的调节因子，定位于有丝分裂中心体。然而，其在中心体的作用尚未完全阐明。在这里，我们报告 LIMK1 耗竭导致多极纺锤体和中心体失焦，表明其参与调节有丝分裂中心体的完整性。LIMK1 可以通过调节纺锤体极中心体蛋白定位来影响中心体的完整性。有趣的是，动力蛋白轻链（LICs）能够挽救 LIMK1 耗竭细胞中观察到的缺陷。我们发现 LICs 是 LIMK1 的潜在新的相互作用伙伴和底物，LIMK1 的磷酸化调节细胞质动力蛋白在中心体蛋白运输中的功能，进而影响有丝分裂纺锤体极完整性。
