Glutamylation of centrosomes ensures their function by recruiting microtubule nucleation factors.

Shi-Rong Hong,Yi-Chien Chuang,Wen-Ting Yang,Chiou-Shian Song,Hung-Wei Yeh,Bing-Huan Wu,I-Hsuan Lin,Po-Chun Chou,Shiau-Chi Chen,Lohitaksh Sharma,Jui-Chen Lu,Rou-Ying Li,Ya-Chu Chang,Kuan-Ju Liao,Hui-Chun Cheng,Won-Jing Wang,Lily Hui-Ching Wang,Yu-Chun Lin
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Abstract

Centrosomes are tubulin-based organelles that undergo glutamylation, a post-translational modification that conjugates glutamic acid residues to tubulins. Although centrosomal glutamylation has been known for several decades, how this modification regulates centrosome structure and function remains unclear. To address this long-standing issue, we developed a method to spatiotemporally reduce centrosomal glutamylation by recruiting an engineered deglutamylase to centrosomes. We found that centrosome structure remains largely unaffected by centrosomal hypoglutamylation. Intriguingly, glutamylation physically recruits, via electrostatic forces, the NEDD1/CEP192/γ-tubulin complex to centrosomes, ensuring microtubule nucleation and proper trafficking of centriolar satellites. The consequent defect in centriolar satellite trafficking leads to reduced levels of the ciliogenesis factor Talpid3, suppressing ciliogenesis. Centrosome glutamylation also promotes proper mitotic spindle formation and mitosis. In summary, our study provides a new approach to spatiotemporally manipulate glutamylation at centrosomes, and offers novel insights into how centrosomes are organized and regulated by glutamylation.
中心体的谷氨酰化通过招募微管成核因子来确保其功能。
中心体是基于微管蛋白的细胞器,经过谷氨酰化,这是一种将谷氨酸残基结合到微管蛋白上的翻译后修饰。虽然中心体谷氨酰化已经知道了几十年,但这种修饰如何调节中心体的结构和功能仍然不清楚。为了解决这个长期存在的问题,我们开发了一种方法,通过向中心体招募工程化的去谷氨酰酶来减少中心体的时空谷氨酰化。我们发现中心体结构在很大程度上不受中心体低谷氨酰化的影响。有趣的是,谷氨酰化通过静电力将NEDD1/CEP192/γ-微管蛋白复合物招募到中心体,确保微管成核和向心卫星的适当运输。由此导致的向心卫星运输缺陷导致纤毛发生因子Talpid3水平降低,从而抑制纤毛发生。中心体谷氨酰化也促进有丝分裂纺锤体形成和有丝分裂。总之,我们的研究提供了一种时空操纵中心体谷氨酰化的新方法,并为中心体如何被谷氨酰化组织和调节提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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