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PMID:23673617

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Citation

Li, MM, Nilsen, A, Shi, Y, Fusser, M, Ding, YH, Fu, Y, Liu, B, Niu, Y, Wu, YS, Huang, CM, Olofsson, M, Jin, KX, Lv, Y, Xu, XZ, He, C, Dong, MQ, Rendtlew Danielsen, JM, Klungland, A and Yang, YG (2013) ALKBH4-dependent demethylation of actin regulates actomyosin dynamics. Nat Commun 4:1832

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.

Links

PubMed PMC3674258 Online version:10.1038/ncomms2863

Keywords

Actins/metabolism; Actomyosin/metabolism; Animals; Carboxy-Lyases/metabolism; Cell Line; Cell Movement; Cytokinesis; Dioxygenases/metabolism; Embryo Loss/metabolism; Embryo Loss/pathology; Gene Deletion; Genetic Complementation Test; Humans; Lysine/metabolism; Methylation; Mice; Models, Biological; Protein Binding

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:ALKB4

located_in

GO:0070938: contractile ring

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ALKB4

located_in

GO:0030496: midbody

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ALKB4

enables

GO:0032451: demethylase activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:ALKB4

GO:0031991: regulation of actomyosin contractile ring contraction

ECO:0000314:

P

regulation of actomyosin activity

complete

HUMAN:ALKB4

enables

GO:0003779: actin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:ALKB4

involved_in

GO:0006482: protein demethylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ALKB4

involved_in

GO:0031032: actomyosin structure organization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ALKB4

part_of

GO:0030496: midbody

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ALKB4

involved_in

GO:0036090: cleavage furrow ingression

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ALKB4

part_of

GO:0070938: contractile ring

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

Notes

See also

References

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