Liro Małgorzata J, Morton Diane G, Rose Lesilee S
Department of Molecular and Cellular Biology and Graduate Program in Biochemistry, Molecular, Cellular and Developmental Biology, University of California, Davis, CA 95616, USA.
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Dev Biol. 2018 Dec 1;444(1):9-19. doi: 10.1016/j.ydbio.2018.08.016. Epub 2018 Sep 10.
The PAR-1 kinase of C. elegans is localized to the posterior of the one-cell embryo and its mutations affect asymmetric spindle placement and partitioning of cytoplasmic components in the first cell cycle. However, par-1 mutations do not cause failure to restrict the anterior PAR polarity complex to the same extent as mutations in the posteriorly localized PAR-2 protein. Further, it has been difficult to examine the role of PAR-1 in subsequent divisions due to the early defects in par-1 mutant embryos. Here we show that the PIG-1 kinase acts redundantly with PAR-1 to restrict the anterior PAR-3 protein for normal polarity in the one-cell embryo. By using a temperature sensitive allele of par-1, which exhibits enhanced lethality when combined with a pig-1 mutation, we have further explored roles for these genes in subsequent divisions. We find that both PIG-1 and PAR-1 regulate spindle orientation in the EMS blastomere of the four-cell stage embryo to ensure that it undergoes an asymmetric division. In this cell, PIG-1 and PAR-1 act in parallel pathways for spindle positioning, PIG-1 in the MES-1/SRC-1 pathway and PAR-1 in the Wnt pathway.
秀丽隐杆线虫的PAR-1激酶定位于单细胞胚胎的后部，其突变会影响第一个细胞周期中纺锤体的不对称定位和细胞质成分的分配。然而，par-1突变不会像后部定位的PAR-2蛋白突变那样导致前部PAR极性复合体受限失败。此外，由于par-1突变胚胎的早期缺陷，很难研究PAR-1在后续分裂中的作用。在这里，我们表明PIG-1激酶与PAR-1冗余作用，以限制前部PAR-3蛋白，从而在单细胞胚胎中实现正常极性。通过使用par-1的温度敏感等位基因，当与pig-1突变结合时，该等位基因表现出增强的致死性，我们进一步探索了这些基因在后续分裂中的作用。我们发现PIG-1和PAR-1都调节四细胞期胚胎的EMS卵裂球中的纺锤体方向，以确保其进行不对称分裂。在这个细胞中，PIG-1和PAR-1在纺锤体定位的平行途径中起作用，PIG-1在MES-1/SRC-1途径中起作用，PAR-1在Wnt途径中起作用。
