ALKBH4-dependent demethylation of actin regulates actomyosin dynamics

TY - JOUR

T1 - ALKBH4-dependent demethylation of actin regulates actomyosin dynamics

AU - Li, M.-M.

AU - Shi, Y.

AU - Niu, Y.

AU - Wu, Y.-S.

AU - Huang, C.-M.

AU - Jin, K.-X.

AU - Lv, Y.

AU - Danielsen, Jannie Michaela Rendtlew

AU - Yang, Y.-G.

AU - Nilsen, A.

AU - Fusser, M.

AU - Olofsson, Maria

AU - Klungland, A.

AU - Ding, Y.-H.

AU - Dong, M.-Q.

AU - Fu, Y.

AU - He, C.

AU - Liu, B.

AU - Xu, X.-Z.

PY - 2013/5/14

Y1 - 2013/5/14

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84878563603&partnerID=8YFLogxK

U2 - 10.1038/ncomms2863

DO - 10.1038/ncomms2863

M3 - Journal article

C2 - 23673617

AN - SCOPUS:84878563603

SN - 2041-1723

VL - 4

JO - Nature Communications

JF - Nature Communications

M1 - 1832

ER -