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-原始提交资料无更新 GPCR信号驱动酵母信息素反应中的细胞极化。响应于 信息素，细胞伸展它们的细胞骨架，并制造交配投射以与交配融合。 搭档在这些交配突起的底部是分隔蛋白结构，用于锚信号 蛋白质和促进膜曲率。隔膜蛋白对有丝分裂也很重要，它们在有丝分裂中发挥重要作用。 在胞质分裂中起关键作用。苯胺类是保守的信号蛋白，负责协调 septin细胞骨架与微管，肌动蛋白和Rho信号在胞质分裂。在这项提案中， 我们试图表征苯胺Boi 1和Boi 2在调节septins过程中的作用。 信息素反应我们假设这有助于极化生长， 通过PP 1磷酸酶的调节信号。在目标1中，我们将研究什么是信号事件 在信息素反应期间的苯胺醛功能的上游。我们将使用活细胞显微镜， 微流控装置，计算图像分析和酵母遗传学，以测试不同的作用， 苯胺结构域在控制信息素反应过程中苯胺的定位。在目标2中， 我们将研究信息素反应中苯胺醛功能的下游效应。使用 与目标1中相同的技术方法，我们将测试苯胺类扰动（突变和 缺失）对下游极性信号传导、隔蛋白动力学、梯度追踪和交配的影响。我们 我预计，我们将发现一个非有丝分裂的作用苯胺在调节septin 细胞骨架我们正在研究的信号网络从酵母到人类都是保守的， 苯胺蛋白在神经元中表达，在癌症中过表达。因此，这些研究将提高我们的 了解苯胺青霉素和塞汀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