Protein Phosphatase 4 Cooperates with Smads to Promote BMP Signaling in Dorsoventral Patterning of Zebrafish Embryos
Protein Phosphatase 4 Cooperates with Smads to Promote BMP Signaling in Dorsoventral Patterning of Zebrafish Embryos
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DOI：
10.1016/j.devcel.2012.03.001
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发表时间：
2012-05-15
影响因子：
11.8
通讯作者：
Meng, Anming
中科院分区：
文献类型：
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作者：
Jia, Shunji;Dai, Fangyan;Meng, Anming
BMP信号在脊椎动物胚胎的背腹图案形成中起关键作用。普遍存在的蛋白磷酸酶4的催化亚基Ppp 4c在脊椎动物胚胎发育中的作用和潜在机制知之甚少。在这里，我们表明，敲低斑马鱼ppp 4cb和/或ppp 4ca抑制胚胎的腹侧发育，也阻断异位Smad 5的腹侧化活性。生化分析表明Ppp 4c是Smad 1/Smad 5的直接结合伴侣和转录共激活因子。为了响应BMP，Ppp 4c被募集到Smad 1占据的启动子，其磷酸酶活性对于抑制HDAC 3活性并因此增强转录激活至关重要。一致地，Hdac 3表达或活性的遗传或化学干扰损害了由ppp 4cb敲低诱导的背侧化表型。我们的结论是，Ppp 4c是一个关键的BMP/Smad信号在斑马鱼胚胎背腹图案形成的正调节器。
BMP signals play pivotal roles in dorsoventral patterning of vertebrate embryos. The role of Ppp4c, the catalytic subunit of ubiquitous protein phosphatase 4, in vertebrate embryonic development and underlying mechanisms is poorly understood. Here, we demonstrate that knockdown of zebrafish ppp4cb and/or ppp4ca inhibits ventral development in embryos and also blocks ventralizing activity of ectopic Smad5. Biochemical analyses reveal that Ppp4c is a direct binding partner and transcriptional coactivator of Smad1/Smad5. In response to BMP, Ppp4c is recruited to the Smad1-occupied promoter, and its phosphatase activity is essential in inhibiting HDAC3 activity and, consequently, potentiating transcriptional activation. Consistently, genetic or chemical interference of Hdac3 expression or activity compromises the dorsalizing phenotype induced by ppp4cb knockdown. We conclude that Ppp4c is a critical positive regulator of BMP/Smad signaling during embryonic dorsoventral pattern formation in zebrafish.