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ALKBH4-dependent demethylation of actin regulates actomyosin dynamics

Li, Ming-Ming; Nilsen, Anja; Shi, Yue; Fusser, Markus; Ding, Yue-He; Fu, Ye; Liu, Bo; Niu, Yamei; Wu, Yong-Sheng and Huang, Chun-Min, et al. (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.

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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
publisher
Nature Publishing Group
external identifiers
  • scopus:84878563603
ISSN
2041-1723
DOI
10.1038/ncomms2863
language
English
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no
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2451a3e6-817a-44ca-bbe0-a4ff524ebf05
date added to LUP
2018-08-27 13:59:53
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2018-10-03 11:50:32
@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>},
  articleno    = {1832},
  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},
  keyword      = {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},
  volume       = {4},
  year         = {2013},
}