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PMID: 23673617 Published · ppublish English Journal Article

ALKBH4-dependent demethylation of actin regulates actomyosin dynamics.

Nature communications ·Vol. 4 ·2013-00-00 ·Pages 1832

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, Yang YG

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.

MeSH Terms
Actins/metabolism Actomyosin/metabolism AlkB Homolog 4, Lysine Demethylase Animals Carboxy-Lyases/metabolism Cell Line Cell Movement Cytokinesis Dioxygenases/metabolism Embryo Loss/metabolism,pathology Gene Deletion Genetic Complementation Test Humans Lysine/metabolism Methylation Mice Models, Biological Protein Binding
Chemicals
Actins Actomyosin Dioxygenases ALKBH4 protein, human ALKBH4 protein, mouse AlkB Homolog 4, Lysine Demethylase Carboxy-Lyases Lysine
Authors & Affiliations
19 authors, click to expand affiliations / ORCID
Li Ming-Ming
Genome Structure and Stability Group, BIG CAS-OSLO Genome Research Cooperation, Disease Genomics and Individualized Medicine Laboratory, Beijing Institute of Genomics, Chinese Academy of Sciences, No. 1-7 Beichen West Road, Chaoyang District, Beijing 100101, China.
Nilsen Anja
Shi Yue
Fusser Markus
Ding Yue-He
Fu Ye
Liu Bo
Niu Yamei
Wu Yong-Sheng
Huang Chun-Min
Olofsson Maria
Jin Kang-Xuan
Lv Ying
Xu Xing-Zhi
He Chuan
Dong Meng-Qiu
Rendtlew Danielsen Jannie M
Klungland Arne
Yang Yun-Gui
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Article Info
Journal
Nature communications
Abbr.
Nat Commun
ISSN
2041-1723
DOI
10.1038/ncomms2863
Published
2013-00-00
Pages
1832
Language
English
Region
England
NLM ID
101528555
PMCID
PMC3674258
Subset
IM
External Links
PubMed source DOI: 10.1038/ncomms2863 PMC Full Text View journal details
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