Abscission is the final stage of cytokinesis, which cleaves the intercellular bridge (ICB) connecting two daughter cells. Abscission requires tight control of the recruitment and polymerization of the Endosomal Protein Complex Required for Transport-III (ESCRT-III) components. We explore the role of post-translational modifications in regulating ESCRT dynamics. We discover that SMYD2 methylates the lysine 6 residue of human CHMP2B, a key ESCRT-III component, at the ICB, impacting the dynamic relocation of CHMP2B to sites of abscission. SMYD2 loss-of-function (genetically or pharmacologically) causes CHMP2B hypomethylation, delayed CHMP2B polymerization and delayed abscission. This is phenocopied by CHMP2B lysine 6 mutants that cannot be methylated. Conversely, SMYD2 gain-of-function causes CHMP2B hypermethylation and accelerated abscission, specifically in cells undergoing cytokinetic challenges, thereby bypassing the abscission checkpoint. Additional experiments highlight the importance of CHMP2B methylation beyond cytokinesis, namely during ESCRT-III-mediated HIV-1 budding. We propose that lysine methylation signaling fine-tunes the ESCRT-III machinery to regulate the timing of cytokinetic abscission and other ESCRT-III dependent functions.

脱落是胞质分裂的最后阶段，它会裂解连接两个子细胞的细胞间桥 (ICB)。脱落需要严格控制运输-III 所需的内体蛋白复合物 (ESCRT-III) 成分的招募和聚合。我们探索翻译后修饰在调节 ESRT 动力学中的作用。我们发现，SMYD2 在 ICB 处甲基化人 CHMP2B 的赖氨酸 6 残基（ESCRT-III 的关键成分），影响 CHMP2B 动态重新定位到脱落位点。 SMYD2 功能丧失（遗传或药理学）导致 CHMP2B 低甲基化、CHMP2B 聚合延迟和脱落延迟。这是无法甲基化的 CHMP2B 赖氨酸 6 突变体的表型复制。相反，SMYD2 功能获得会导致 CHMP2B 过度甲基化并加速脱落，特别是在经历细胞因子挑战的细胞中，从而绕过脱落检查点。其他实验强调了 CHMP2B 甲基化在胞质分裂之外的重要性，即在 ESCRT-III 介导的 HIV-1 出芽期间。我们认为赖氨酸甲基化信号传导可以微调 ESCRT-III 机制来调节细胞分裂的时间和其他 ESCRT-III 依赖性功能。