MAPK3/1 (ERK1/2) and Myosin Light Chain Kinase in Mammalian Eggs Affect Myosin-II Function and Regulate the Metaphase II State in a Calcium- and Zinc-Dependent Manner.
MAPK3/1 (ERK1/2) and Myosin Light Chain Kinase in Mammalian Eggs Affect Myosin-II Function and Regulate the Metaphase II State in a Calcium- and Zinc-Dependent Manner.
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哺乳动物卵中的 MAPK3/1 (ERK1/2) 和肌球蛋白轻链激酶影响肌球蛋白 II 功能并以钙和锌依赖性方式调节中期 II 状态。
DOI：
10.1095/biolreprod.114.127027
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发表时间：
2015
影响因子：
3.6
通讯作者：
Evans,JaniceP
中科院分区：
文献类型：
--
作者：
McGinnis,LaurenA;Lee,HyoJ;Robinson,DouglasN;Evans,JaniceP
脊椎动物的卵子在减数分裂中期被阻滞，这种状态被称为细胞生长抑制因子阻滞。维持这种停滞直到受精的时间，然后受精诱导退出中期II是生殖成功的关键。减数分裂停滞和退出的另一个关键方面是中期II纺锤体的调节，中期II纺锤体必须在中期II期间适当地定位在卵皮质附近，然后进入成功的不对称胞质分裂以产生第二极体。本研究探讨了有丝分裂原活化蛋白激酶MAPK 3和MAPK 1（也称为ERK 1/2）作为哺乳动物卵子生物学这两个相关方面的调节剂，特别是测试这种MAPK途径是否影响肌球蛋白-II功能，以及肌球蛋白-II扰动是否会产生一些与MAPK途径扰动相同的效果。用U 0126抑制MEK 1/2-MAPK途径导致磷酸化肌球蛋白调节轻链（pMRLC）水平降低，并引起皮质张力降低，这是用肌球蛋白轻链激酶（MLCK）抑制剂ML-7处理所模拟的效果。这些数据表明MAPK途径在卵中起作用的一种机制是通过影响肌球蛋白-II的功能。我们进一步表明，MAPK或MLCK抑制诱导正常皮质纺锤体定位或孤雌卵激活的损失。这种孤雌生殖依赖于细胞溶质和细胞外钙，可以通过用锌超负荷卵来拯救，这表明MLCK或MAPK途径的抑制作用与离子稳态失调有关。
Vertebrate eggs are arrested at metaphase of meiosis II, a state classically known as cytostatic factor arrest. Maintenance of this arrest until the time of fertilization and then fertilization-induced exit from metaphase II are crucial for reproductive success. Another key aspect of this meiotic arrest and exit is regulation of the metaphase II spindle, which must be appropriately localized adjacent to the egg cortex during metaphase II and then progress into successful asymmetric cytokinesis to produce the second polar body. This study examined the mitogen-activated protein kinases MAPK3 and MAPK1 (also known as ERK1/2) as regulators of these two related aspects of mammalian egg biology, specifically testing whether this MAPK pathway affected myosin-II function and whether myosin-II perturbation would produce some of the same effects as MAPK pathway perturbation. Inhibition of the MEK1/2-MAPK pathway with U0126 leads to reduced levels of phosphorylated myosin-regulatory light chain (pMRLC) and causes a reduction in cortical tension, effects that are mimicked by treatment with the myosin light chain kinase (MLCK) inhibitor ML-7. These data indicate that one mechanism by which the MAPK pathway acts in eggs is by affecting myosin-II function. We further show that MAPK or MLCK inhibition induces loss of normal cortical spindle localization or parthenogenetic egg activation. This parthenogenesis is dependent on cytosolic and extracellular calcium and can be rescued by hyperloading eggs with zinc, suggesting that these effects of inhibition of MLCK or the MAPK pathway are linked with dysregulation of ion homeostasis.