AI Article Synopsis
- The study investigates how post-transcriptional modifications, specifically demethylation of actin by ALKBH4, affect actomyosin dynamics, a crucial process for cell movement and division.
- ALKBH4 removes a methyl group from the K84 position on actin; its absence leads to improper actin-myosin interactions, impaired cell functions like cytokinesis, and increased levels of methylated actin.
- Mice lacking the ALKBH4 gene show severe developmental issues and early embryonic lethality, indicating the importance of this modification in embryonic development and cellular processes.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674258 | PMC |
| http://dx.doi.org/10.1038/ncomms2863 | DOI Listing |
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