Control of cell morphogenesis and cell growth by conserved NDR kinase Orb6

细胞形态发生缺陷促进癌症和神经系统等疾病的发生 精神错乱。细胞极性丧失和组织结构破坏是癌症的常见组织学特征， 在组织结构改变中起着重要作用。虽然已经取得了实质性的进展， 协调细胞形态和细胞生长的分子机制仍然知之甚少。长的- 我们实验室的学期目标是了解控制细胞形状出现的细胞功能，以及在 特别是协调细胞极性和细胞生长的信号网络。 保守的NDR激酶在控制细胞形态和细胞增殖中起关键作用 从酵母菌到哺乳动物的几种生物。目前，人们对这些问题的了解非常有限。 这种保守的激酶及其靶标的细胞功能。我们之前已经发现，分裂酵母 NDR激酶Orb6在空间上调节CDC42 GTP酶的活性，CDC42 GTP酶是一个关键的形态控制因子。最近， 我们已经证明，Orb6激酶也负向调节mRNA的降解和翻译抑制， 促进极化细胞生长。利用基因组规模和蛋白质组学的方法，我们已经鉴定出了新的 Orb6激酶的靶标，并发现Orb6激酶在促进细胞适应和修复中的新作用 静止期按时间顺序排列的寿命。本项目的目标是确定 NDR激酶在酵母和酵母中调节细胞形状、促进细胞生长和培养细胞弹性 人类细胞。在特定的Aim1中，我们将定义NDR激酶如何磷酸化关键底物以使细胞 形状浮现。在特定的AIM2中，我们将确定NDR激酶是如何调节特定的mRNA结合的 控制极化细胞生长的蛋白质。在特定的Aim3中，我们将确定NDR激酶在使能中的作用 另一种生理状态，从活跃的细胞生长到静止的细胞，以促进细胞的弹性。

Defects in cell morphogenesis promote the onset of diseases such as cancer and neurological disorders. Loss of cell polarity and disruption of tissue architecture is a common histological feature in cancer, playing an important role in the alteration of tissue organization. Although substantial progress has been made, the molecular mechanisms coordinating cell morphology and cell growth are still poorly understood. The long- term goal of our laboratory is to understand the cellular functions that govern cell shape emergence, and in particular the signaling networks that coordinate cell polarity with cell growth. The conserved NDR kinase plays a key role in the control of cell morphology and cell proliferation in several organisms ranging from yeast to mammals. Currently, there is a very limited understanding of the cellular functions of this conserved kinase and of its targets. We have previously discovered that fission yeast NDR kinase Orb6 spatially regulates the activity of Cdc42 GTPase, a key morphology control factor. Recently, we have shown that Orb6 kinase also negatively regulates mRNA degradation and translational repression, promoting polarized cell growth. Using genomic-scale and proteomic approaches we have identified novel targets of Orb6 kinase, and discovered a novel role for Orb6 kinase in promoting cell adaptation and chronological lifespan during quiescence. The objective of this project is to define the mechanisms whereby NDR kinase spatially regulates cell shape, promotes cell growth and foster cell resilience in both yeast and human cells. In Specific Aim1, we will define how NDR kinase phosphorylates key substrates to enable cell shape emergence. In Specific Aim2, we will determine how NDR kinase regulates specific mRNA binding proteins to control polarized cell growth. In Specific Aim3, we will establish the role of NDR kinase in enabling alternative physiological states, from active cell growth to cell quiescence, to promote cell resilience.