ALKBH4-dependent demethylation of actin regulates actomyosin dynamics
(2013) In Nature Communications 4.- Abstract
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.... (More)
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.
(Less)
- author
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- keywords
- Actins/metabolism, Actomyosin/metabolism, AlkB Homolog 4, Lysine Demethylase, Animals, Carboxy-Lyases/metabolism, Cell Line, Cell Movement, Cytokinesis, Dioxygenases/metabolism, Embryo Loss/metabolism, Gene Deletion, Genetic Complementation Test, Humans, Lysine/metabolism, Methylation, Mice, Models, Biological, Protein Binding
- in
- Nature Communications
- volume
- 4
- article number
- 1832
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:23673617
- scopus:84878563603
- ISSN
- 2041-1723
- DOI
- 10.1038/ncomms2863
- language
- English
- LU publication?
- no
- id
- 2451a3e6-817a-44ca-bbe0-a4ff524ebf05
- date added to LUP
- 2018-08-27 13:59:53
- date last changed
- 2024-05-27 15:28:53
@article{2451a3e6-817a-44ca-bbe0-a4ff524ebf05, abstract = {{<p>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.</p>}}, author = {{Li, Ming-Ming and Nilsen, Anja and Shi, Yue and Fusser, Markus and Ding, Yue-He and Fu, Ye and Liu, Bo and Niu, Yamei and Wu, Yong-Sheng and Huang, Chun-Min and Olofsson, Maria and Jin, Kang-Xuan and Lv, Ying and Xu, Xing-Zhi and He, Chuan and Dong, Meng-Qiu and Rendtlew Danielsen, Jannie M and Klungland, Arne and Yang, Yun-Gui}}, issn = {{2041-1723}}, keywords = {{Actins/metabolism; Actomyosin/metabolism; AlkB Homolog 4, Lysine Demethylase; Animals; Carboxy-Lyases/metabolism; Cell Line; Cell Movement; Cytokinesis; Dioxygenases/metabolism; Embryo Loss/metabolism; Gene Deletion; Genetic Complementation Test; Humans; Lysine/metabolism; Methylation; Mice; Models, Biological; Protein Binding}}, language = {{eng}}, publisher = {{Nature Publishing Group}}, series = {{Nature Communications}}, title = {{ALKBH4-dependent demethylation of actin regulates actomyosin dynamics}}, url = {{http://dx.doi.org/10.1038/ncomms2863}}, doi = {{10.1038/ncomms2863}}, volume = {{4}}, year = {{2013}}, }