Histone deacetylase 6 regulates cytokinesis and erythrocyte enucleation through deacetylation of formin protein mDia2.
Histone deacetylase 6 regulates cytokinesis and erythrocyte enucleation through deacetylation of formin protein mDia2.
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DOI：
10.3324/haematol.2016.161513
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发表时间：
2017-06
期刊：
影响因子：
10.1
通讯作者：
Qiu Y
中科院分区：
文献类型：
--
作者：
Li X;Mei Y;Yan B;Vitriol E;Huang S;Ji P;Qiu Y
肌动蛋白mDia2通过其促进肌动蛋白丝的成核和伸长的能力在许多细胞过程中起关键作用。在成红细胞中，这包括通过调节收缩性肌动蛋白环的形成来控制胞质分裂和去核。在这里，我们报告了一种新的机制，如何mDia2的调节：通过乙酰化和脱乙酰化在赖氨酸970的同源性2域。小鼠成红细胞中乙酰基模拟mDia2突变体的异位表达足以废除在卵裂沟处的收缩性肌动蛋白环形成以及随后的红细胞胞质分裂和去核。我们还确定了II类组蛋白脱乙酰基酶6脱乙酰化，随后激活mDia2。敲低或抑制组蛋白脱乙酰基酶6损害收缩肌动蛋白环的形成，和非乙酰基模拟mDia2突变体的表达恢复收缩肌动蛋白环和抢救去核损伤。除了揭示mDia2调控中的一个新步骤外，这项研究还可能揭示一种新的formin介导的肌动蛋白组装调控机制，因为K970乙酰化位点在Dia蛋白中是保守的
The formin protein 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 the 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. We also identified that class II histone deacetylase 6 deacetylates and subsequently activates mDia2. Knockdown 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 impairment of enucleation. In addition to revealing a new 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