Alternative splicing of (ppp1r12a/mypt1) in zebrafish produces a novel myosin phosphatase targeting subunit.
Alternative splicing of (ppp1r12a/mypt1) in zebrafish produces a novel myosin phosphatase targeting subunit.
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DOI：
10.1016/j.gene.2018.06.092
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发表时间：
2018-10-30
期刊：
影响因子：
3.5
通讯作者：
Weiser DC
中科院分区：
文献类型：
--
作者：
LaFlamme A;Young KE;Lang I;Weiser DC
肌球蛋白磷酸酶是一种进化保守的肌球蛋白收缩调节因子，由一个调节亚基(Mypt1)和一个催化亚基(PP1)组成。斑马鱼已成为研究肌球蛋白磷酸酶在形态发生和胚胎发育中的遗传和细胞生理作用的理想模式生物。我们从斑马鱼中发现并鉴定了Mypt1的一个新的剪接变异体(ppp1r12a-tw202)，它在早期胚胎发育中广泛表达。重要的是，突变的等位基因和反义吗啉已被用来证明Mypt1在早期发育中的重要作用，不仅扰乱了较长的剪接变体，而且还干扰了TV202。Ppp1r12a-tw202(Mypt1-202)的蛋白产物含有PP1结合的N末端，但缺少调控的C末端，该末端含有两个高度保守的抑制性磷酸化位点。我们观察到TV202的蛋白产物组装了一种不受Zipk等激酶抑制的结构性活性肌球蛋白磷酸酶。因此，我们认为Mypt1-202在斑马鱼发育早期维持基线MLC2去磷酸化和肌球蛋白松弛中起重要作用。
Myosin phosphatase is an evolutionarily conserved regulator of actomyosin contractility, comprised of a regulatory subunit (Mypt1), and a catalytic subunit (PP1). Zebrafish has become an ideal model organism for the study of the genetic and cell physiological role of the myosin phosphatase in morphogenesis and embryonic development. We identified and characterized a novel splice variant of Mypt1 (ppp1r12a-tv202) from zebrafish, which is widely expressed during early embryonic development. Importantly, mutant alleles and antisense morpholinos that have been used to demonstrate the important role of Mypt1 in early development, not only disrupt the longer splice variants, but also tv202. The protein product of ppp1r12a-tv202 (Mypt1–202) contains the PP1-binding N-terminus, but lacks the regulatory C-terminus, which contains two highly conserved inhibitory phosphorylation sites. We observed that the protein product of tv202 assembled a constitutively active myosin phosphatase uninhibited by kinases such as Zipk. Thus, we propose that Mypt1–202 plays an important role in maintaining baseline Mlc2 dephosphorylation and actomyosin relaxation during early zebrafish development.
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