Supplement Request: The Role of Anillins in Gradient Tracking

补充请求：Anillins 在梯度跟踪中的作用

• 批准号: 10799109
• 负责人: Joshua Brian Kelley
• 金额: $ 9.9万
• 依托单位: UNIVERSITY OF MAINE ORONO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10799109
• 关键词: Actins; Cell Shape; Cell division; Cells; Cytokinesis; Cytoskeleton; Event; G Protein-Coupled Receptor Signaling; Growth; Health; Human; Image Analysis; Malignant Neoplasms; Membrane; Microfluidic Microchips; Microtubules; Mitosis; Mutation; Neurons; Partner in relationship; Pheromone; Phosphoric Monoester Hydrolases; Play; Proteins; Regulation; Role; Shapes; Signal Transduction; Signaling Protein; Structure; Testing; Update; Yeasts; anillin; base; cell motility; live cell microscopy; overexpression; polarized cell; response; rho; yeast genetics

Project Summary - No updates from original submission GPCR signaling drives cell polarization in the yeast pheromone response. In response to pheromone, cells polarize their cytoskeleton and make a mating projection to fuse with a mating partner. At the base of these mating projections are septin structures, serving to anchor signaling proteins and promote membrane curvature. Septins are also important for mitosis where they play a key role in cytokinesis. Anillins are conserved signaling proteins responsible for coordinating the septin cytoskeleton with microtubules, actin, and Rho signaling during cytokinesis. In this proposal, we seek to characterize the role of the anillins Boi1 and BOi2 in regulating septins during the pheromone response. We hypothesize that this contributes to polarized growth and that the anillins signal through regulation of the PP1 phosphatase. In Aim 1, we will examine what signaling events lie upstream of anillin function during the pheromone response. We will use live cell microscopy in microfluidic devices, computational image analysis and yeast genetics to test the role of different anillin domains in controlling the localization of the anillins during the pheromone response. In Aim 2, we will examine the downstream effects of anillin function in the pheromone response. Using the same technical approaches as in Aim 1, we will test the effect of anillins perturbation (mutations and deletions) on downstream polarity signaling, septin dynamics, gradient tracking, and mating. We anticipate that we will discover a non-mitotic role for anillins in the regulation of the septin cytoskeleton. The signaling networks we are studying are conserved from yeast to humans, where anillins are expressed in neurons and overexpressed in cancer. Thus, these studies will enhance our understanding of anillin and septin roles in human health.

项目摘要 - 原始提交中没有更新 GPCR信号传导驱动酵母信息素反应中的细胞极化。响应 信息素，细胞使其细胞骨架两极，并与配合 伙伴。在这些交配预测的底部是septin结构，用于锚定信号 蛋白质并促进膜曲率。 Septins对于有丝分裂也很重要 细胞因子的关键作用。阿尼林是负责协调的保守信号蛋白 septin细胞骨架，带有微管，肌动蛋白和Rho信号传导。在此提案中， 我们试图表征Anillins Boi1和Boi2在调节septins中的作用 信息素反应。我们假设这有助于两极分化的生长和anillins 通过调节PP1磷酸酶的信号。在AIM 1中，我们将检查哪些信号事件在 在信息素反应期间阿尼蛋白功能的上游。我们将在 微流体设备，计算图像分析和酵母遗传学测试不同的作用 在信息素反应过程中控制anillin的定位时，阿尼蛋白结构域。在AIM 2中， 我们将检查Anillin功能在信息素反应中的下游效应。使用 与AIM 1相同的技术方法，我们将测试Anillins扰动的效果（突变和 删除）在下游极性信号，septin动力学，梯度跟踪和交配上。我们 预计我们将发现阿尼林在septin调节中的非丝裂作用 细胞骨架。我们正在研究的信号网络是从酵母到人的保守的，那里 阿尼林在神经元中表达，并在癌症中表达过表达。因此，这些研究将增强我们的 了解阿尼林和隔丁在人类健康中的作用。

项目成果

Phosphorylation of RGS regulates MAP kinase localization and promotes completion of cytokinesis.

• DOI: 10.26508/lsa.202101245
• 发表时间: 2022-10
• 期刊: LIFE SCIENCE ALLIANCE
• 影响因子: 4.4
• 作者: Simke, William C.;Johnson, Cory P.;Hart, Andrew J.;Mayhue, Sari;Craig, P. Lucas;Sojka, Savannah;Kelley, Joshua B.
• 通讯作者: Kelley, Joshua B.

Variable penetrance of Nab3 granule accumulation quantified by a new tool for high-throughput single-cell granule analysis.

• DOI: 10.1007/s00294-022-01234-2
• 发表时间: 2022-08
• 期刊: Current genetics
• 影响因子: 2.5