Casein kinase 1 alpha regulates chromosome congression and separation during mouse oocyte meiotic maturation and early embryo development.
Casein kinase 1 alpha regulates chromosome congression and separation during mouse oocyte meiotic maturation and early embryo development.
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酪蛋白激酶 1 α 在小鼠卵母细胞减数分裂成熟和早期胚胎发育过程中调节染色体的聚集和分离。
DOI：
10.1371/journal.pone.0063173
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Liang CG
中科院分区：
文献类型：
--
作者：
Wang L;Lu A;Zhou HX;Sun R;Zhao J;Zhou CJ;Shen JP;Wu SN;Liang CG
酪蛋白激酶I α（CK 1 α）是丝氨酸/苏氨酸蛋白激酶的一个成员，普遍存在于所有真核生物中。在哺乳动物中，CK 1 α调节有丝分裂从间期到中期的转变。然而，很少有人知道它在减数分裂中的作用。在这里，我们检测了Ck 1 α mRNA和蛋白质的表达，以及其在小鼠卵母细胞从生发泡到1细胞晚期阶段的亚细胞定位。结果表明，在细胞分裂中期，CK 1 α的表达水平升高。免疫组化结果显示，在卵母细胞减数分裂成熟和早期胚胎发育过程中，CK 1 α与浓缩染色体共定位。我们使用功能丧失的方法，通过使用CK 1 α特异性吗啉代注射来阻断CK 1 α的功能。这种功能性阻断导致极体1（PB 1）挤出失败、染色体错位和MII板增厚。我们进一步发现，D4476，一种特异性和有效的CK 1抑制剂，降低PB 1的挤出速率。此外，D4476还导致巨大极体排出、卵母细胞前MI停滞、染色体聚集失败和胚胎发育潜能受损。此外，我们还使用了CK 1 α的别构激活剂pyrvinium pamoate（PP）来增强卵母细胞中CK 1 α的活性。补充PP可导致卵母细胞减数分裂失败，严重的聚集异常和染色体排列不齐。综上所述，我们的研究首次表明，CK 1 α是卵母细胞减数分裂成熟和早期胚胎发育过程中染色体排列和分离所必需的。
Casein kinase I alpha (CK1α) is a member of serine/threonine protein kinase, generally present in all eukaryotes. In mammals, CK1α regulates the transition from interphase to metaphase in mitosis. However, little is known about its role in meiosis. Here we examined Ck1α mRNA and protein expression, as well as its subcellular localization in mouse oocytes from germinal vesicle to the late 1-cell stage. Our results showed that the expression level of CK1α was increased in metaphase. Immunostaining results showed that CK1α colocalized with condensed chromosomes during oocyte meiotic maturation and early embryo development. We used the loss-of-function approach by employing CK1α specific morpholino injection to block the function of CK1α. This functional blocking leads to failure of polar body 1 (PB1) extrusion, chromosome misalignment and MII plate incrassation. We further found that D4476, a specific and efficient CK1 inhibitor, decreased the rate of PB1 extrusion. Moreover, D4476 resulted in giant polar body extrusion, oocyte pro-MI arrest, chromosome congression failure and impairment of embryo developmental potential. In addition, we employed pyrvinium pamoate (PP), an allosteric activator of CK1α, to enhance CK1α activity in oocytes. Supplementation of PP induced oocyte meiotic maturation failure, severe congression abnormalities and misalignment of chromosomes. Taken together, our study for the first time demonstrates that CK1α is required for chromosome alignment and segregation during oocyte meiotic maturation and early embryo development.
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