ALKBH4-dependent demethylation of actinregulates actomyosin dynamics

摘要

Regulation of actomyosin dynamics by post-transcriptional modifications in cytoplasmic actinis still poorly understood. Here we demonstrate that dioxygenase ALKBH4-mediateddemethylation of a monomethylated site in actin (K84me1) regulates actin–myosin interactionand actomyosin-dependent processes such as cytokinesis and cell migration. ALKBH4-deficient cells display elevated K84me1 levels. Non-muscle myosin II only interacts withunmethylated actin and its proper recruitment to and interaction with actin depend onALKBH4. ALKBH4 co-localizes with the actomyosin-based contractile ring and midbody viaassociation with methylated actin. ALKBH4-mediated regulation of actomyosin dynamics iscompletely dependent on its catalytic activity. Disorganization of cleavage furrow componentsand multinucleation associated with ALKBH4 deficiency can all be restored byreconstitution with wild-type but not catalytically inactive ALKBH4. Similar to actin andmyosin knock-out mice, homozygous Alkbh4 mutant mice display early embryonic lethality.These findings imply that ALKBH4-dependent actin demethylation regulates actomyosinfunction by promoting actin-non-muscle myosin II interaction.