- 1 Department of Anatomy and Cell Biology, College of Medicine, University of Florida, Gainesville, USA;
- 2 Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, USA;
- 3 Dept of Biochemistry and Molecular Biology,College of Medicine,University of Florida,Gainesville,USA
- ↵* Corresponding author; email:
The formin mDia2 plays a critical role in a number of cellular processes through its ability to promote nucleation and elongation of actin filaments. In erythroblasts, this includes control of cytokinesis and enucleation by regulating contractile actin ring formation. Here, we report a novel mechanism of how mDia2 is regulated: through acetylation and deacetylation at lysine 970 in formin homology 2 domain. Ectopic expression of an acetyl-mimic mDia2 mutant in mouse erythroblasts is sufficient to abolish contractile actin ring formation at the cleavage furrow and subsequent erythrocyte cytokinesis and enucleation. Further, we have identified that Class II histone deacetylase 6 deacetylates and subsequently activates mDia2. Knock down or inhibition of histone deacetylase 6 impairs contractile actin ring formation, and expression of a non-acetyl-mimic mDia2 mutant restores the contractile actin ring and rescues the loss of enucleation. In addition to revealing a novel step in mDia2 regulation, this study may unveil a novel regulatory mechanism of formin mediated actin assembly, since the K970 acetylation site is conserved among Dia proteins.
- Received December 1, 2016.
- Accepted February 27, 2017.
- Copyright © 2017, Ferrata Storti Foundation