ALKBH4-dependent demethylation of actin regulates actomyosin dynamics
| Autor: | Anja Nilsen, Maria Olofsson, Chuan He, Kang-Xuan Jin, Ye Fu, Bo Liu, Xingzhi Xu, Ming-Ming Li, Yuehe Ding, Jannie M. Rendtlew Danielsen, Markus Fusser, Yue Shi, Yamei Niu, Yun-Gui Yang, Arne Klungland, Meng-Qiu Dong, Yong-Sheng Wu, Chun-Min Huang, Ying Lv |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
AlkB Homolog 4
Lysine Demethylase Carboxy-Lyases General Physics and Astronomy Arp2/3 complex macromolecular substances Microfilament Methylation Models Biological General Biochemistry Genetics and Molecular Biology Article Cell Line Dioxygenases Mice Cell Movement Myosin Animals Humans Cleavage furrow Actin Cytokinesis Multidisciplinary biology Lysine Genetic Complementation Test Actin remodeling General Chemistry Actomyosin Actins Cell biology Midbody Biochemistry biology.protein Embryo Loss Gene Deletion Protein Binding |
| Zdroj: | Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Regulation of actomyosin dynamics by post-transcriptional modifications in cytoplasmic actin is still poorly understood. Here we demonstrate that dioxygenase ALKBH4-mediated demethylation of a monomethylated site in actin (K84me1) regulates actin–myosin interaction and actomyosin-dependent processes such as cytokinesis and cell migration. ALKBH4-deficient cells display elevated K84me1 levels. Non-muscle myosin II only interacts with unmethylated actin and its proper recruitment to and interaction with actin depend on ALKBH4. ALKBH4 co-localizes with the actomyosin-based contractile ring and midbody via association with methylated actin. ALKBH4-mediated regulation of actomyosin dynamics is completely dependent on its catalytic activity. Disorganization of cleavage furrow components and multinucleation associated with ALKBH4 deficiency can all be restored by reconstitution with wild-type but not catalytically inactive ALKBH4. Similar to actin and myosin knock-out mice, homozygous Alkbh4 mutant mice display early embryonic lethality. These findings imply that ALKBH4-dependent actin demethylation regulates actomyosin function by promoting actin-non-muscle myosin II interaction. The division of a single eukaryotic cell into two requires actomyosin-dependent contraction. Here the authors show that lysine methylation of actin inhibits contractility during cytokinesis by blocking its association with myosin, and this modification is reversed at the contractile ring by the demethylase ALKBH4. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|