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Updated: Oct 18, 2025

Reconstitution of Basic Mitotic Spindles in Spherical Emulsion Droplets
Published on: August 13, 2016
Dynamic crotonylation of EB1 by TIP60 ensures accurate spindle positioning in mitosis
Xiaoyu Song1,2, Fengrui Yang1,2, Xu Liu1,2
1MOE Key Laboratory for Cellular Dynamics and Hefei National Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China.
Abstract:
Spindle position control is essential for cell fate determination and organogenesis. Early studies indicate the essential role of the evolutionarily conserved Gαi/LGN/NuMA network in spindle positioning. However, the regulatory mechanisms that couple astral microtubules dynamics to the spindle orientation remain elusive. Here we delineated a new mitosis-specific crotonylation-regulated astral microtubule-EB1-NuMA interaction in mitosis. EB1 is a substrate of TIP60, and TIP60-dependent crotonylation of EB1 tunes accurate spindle positioning in mitosis. Mechanistically, TIP60 crotonylation of EB1 at Lys66 forms a dynamic link between accurate attachment of astral microtubules to the lateral cell cortex defined by NuMA-LGN and fine tune of spindle positioning. Real-time imaging of chromosome movements in HeLa cells expressing genetically encoded crotonylated EB1 revealed the importance of crotonylation dynamics for accurate control of spindle orientation during metaphase-anaphase transition. These findings delineate a general signaling cascade that integrates protein crotonylation with accurate spindle positioning for chromosome stability in mitosis.
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