Jiangsu Key Laboratory for Microbes and Functional Genomics, Jiangsu Engineering and Technology Research Center for Microbiology, College of Life Sciences, Nanjing Normal University, Nanjing, 210046, China.
Cell Signal. 2011 Nov;23(11):1750-7. doi: 10.1016/j.cellsig.2011.06.009. Epub 2011 Jun 30.
Establishment and maintenance of cell polarity are coordinated by signaling pathways such as NDR (nuclear Dbf2-related) protein-kinase signaling and calcium signaling pathway. The NDR family of kinase is structurally related to the human myotonic dystrophy kinase, which, when impaired, confers a disease that involves changes in cytoarchitecture and ion homeostasis. CotA kinase, a member of the NDR protein kinase family, forms a complex with MobB to regulate cell polarized growth in Aspergillus nidulans. Our previous study demonstrated that mobB/cotA defects could be suppressed by the osmotic stress in the presence of external calcium. In this study, via the genetic and molecular approach, we further demonstrated that Ca(2+)-permeable stretch-activated nonselective cation channel-MidA, calcium/calmodulin-dependent protein phosphatase catalatic subunit-CnaA and external calcium, but not voltage-gated calcium channel homolog-CchA, were required for the osmotic stabilizer-coupled suppression. The up-regulation of calcium/calcineurin signaling pathway induced by osmotic stress might be the reason for bypassing the requirements of NDR kinase complex, which is otherwise necessary for polar morphogenesis. Our results suggest that calcium-calcineurin signaling pathway coordinates with MobB/CotA kinase complex in regulating polarity growth via maintaining cellular calcium homeostasis. However, CchA may act differently as other components in calcium signaling pathway in Aspergillus nidulans. These findings provide an excellent opportunity to identify the potential pathway linking NDR protein-kinase network to calcium signaling pathway.
细胞极性的建立和维持是通过信号通路来协调的，如 NDR（核 Dbf2 相关）蛋白激酶信号通路和钙信号通路。NDR 激酶家族与人类肌强直性营养不良激酶在结构上相关，当该激酶受损时，会导致涉及细胞结构和离子稳态变化的疾病。CotA 激酶是 NDR 蛋白激酶家族的一员，与 MobB 形成复合物，调节 Aspergillus nidulans 细胞的极化生长。我们之前的研究表明，在存在外部钙的情况下，渗透压胁迫可以抑制 mobB/cotA 缺陷。在这项研究中，通过遗传和分子方法，我们进一步证明了钙通透性拉伸激活的非选择性阳离子通道 MidA、钙/钙调蛋白依赖性蛋白磷酸酶催化亚基 CnaA 和外部钙，而不是电压门控钙通道同源物 CchA，是渗透压稳定剂偶联抑制所必需的。渗透压胁迫引起的钙/钙调神经磷酸酶信号通路的上调可能是绕过 NDR 激酶复合物要求的原因，否则 NDR 激酶复合物是极性形态发生所必需的。我们的结果表明，钙-钙调神经磷酸酶信号通路通过维持细胞内钙稳态与 MobB/CotA 激酶复合物协调调节极性生长。然而，CchA 在 Aspergillus nidulans 中的钙信号通路中可能与其他成分作用不同。这些发现为确定将 NDR 蛋白激酶网络与钙信号通路联系起来的潜在途径提供了极好的机会。
