Department of Systems Biology, Yonsei University, Seodaemun-gu, Seoul 03722, South Korea.
Mol Biol Cell. 2019 Oct 1;30(21):2651-2658. doi: 10.1091/mbc.E18-12-0822. Epub 2019 Sep 4.
Wound closure in the larval epidermis mainly involves nonproliferative, endocyling epithelial cells. Consequently, it is largely mediated by cell growth and migration. We discovered that both cell growth and migration in require the cochaperone-encoding gene . Larvae lacking in the epidermis failed to close wounds, and the cells of the epidermis failed to change cell shape and polarize. Likewise, wound-induced cell growth was significantly reduced, and correlated with a reduction in the size of the cell nucleus. The c-Jun N-terminal kinase (JNK) pathway, which is essential for wound closure, was not typically activated in injured knockdown larvae. In addition, JNK, Hep, Mkk4, and Tak1 protein levels were reduced, consistent with previous reports showing that Cdc37 is important for the stability of various client kinases. Protein levels of the integrin β subunit and its wound-induced protein expression were also reduced, reflecting the disruption of JNK activation, which is crucial for expression of integrin β during wound closure. These results are consistent with a role of Cdc37 in maintaining the stability of the JNK pathway kinases, thus mediating cell growth and migration during wound healing.
幼虫表皮的伤口闭合主要涉及非增殖性的、有丝分裂后上皮细胞。因此，它主要通过细胞生长和迁移来介导。我们发现， 所需的伴侣蛋白编码基因 对于细胞生长和迁移都是必需的。表皮中缺乏 的 幼虫无法闭合伤口，表皮细胞无法改变细胞形状和极化。同样，伤口诱导的细胞生长显著减少，并且与核体积的减小相关。c-Jun N 端激酶（JNK）途径对于伤口闭合是必需的，但在受伤的 敲低幼虫中通常未被激活。此外，JNK、Hep、Mkk4 和 Tak1 蛋白水平降低，与之前的报道一致，表明 Cdc37 对于各种客户激酶的稳定性很重要。整合素 β 亚基及其伤口诱导蛋白表达的蛋白水平也降低，反映了 JNK 激活的中断，这对于伤口闭合过程中整合素 β 的表达至关重要。这些结果与 Cdc37 在维持 JNK 途径激酶稳定性中的作用一致，从而介导 伤口愈合过程中的细胞生长和迁移。
