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ALKBH4-dependent demethylation of actin regulates actomyosin dynamics.
- Source :
-
Nature communications [Nat Commun] 2013; Vol. 4, pp. 1832. - Publication Year :
- 2013
-
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. 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.
- Subjects :
- AlkB Homolog 4, Lysine Demethylase
Animals
Cell Line
Cell Movement
Cytokinesis
Embryo Loss metabolism
Embryo Loss pathology
Gene Deletion
Genetic Complementation Test
Humans
Lysine metabolism
Methylation
Mice
Models, Biological
Protein Binding
Actins metabolism
Actomyosin metabolism
Carboxy-Lyases metabolism
Dioxygenases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 4
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 23673617
- Full Text :
- https://doi.org/10.1038/ncomms2863