Mechanisms behind Rapid Tip Growth

尖端快速增长背后的机制

• 批准号: 8412759
• 负责人: Zhenbiao Yang
• 金额: $ 26.61万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8412759
• 关键词: Actins; Address; Apical; Arabidopsis; Autocrine Communication; Back; Biological; Biological Models; Calcium; Cell Surface Receptors; Cell Wall; Cell membrane; Cells; Clathrin; Clear Cell; Computer Simulation; Coupled; Data; Destinations; Development; Drug Targeting; Endocytosis; Endocytosis Pathway; Environment; Exocytosis; Feedback; Female; Fertilization; Funding; Genetic; Genetic Screening; Goals; Growth; Health; Human; Hyphae; Invaded; Laboratories; Length; Ligands; Link; Mechanics; Mediating; Microfilaments; Modeling; Molecular; Mycelium; Neurons; Nutrient; Pectins; Phosphotransferases; Plants; Pollen Tube; Principal Investigator; Process; Regulation; Research; Role; Series; Shoulder; Signal Transduction; Speed; System; Testing; Time; Tissues; Travel; Vesicle; Work; base; cell growth; design; extracellular; fungus; inhibitor/antagonist; insight; latrunculin B; mathematical model; mutant; novel; pathogen; prevent; rho; rho GTP-Binding Proteins; spatiotemporal; sperm cell; targeted delivery

DESCRIPTION (provided by applicant): The long-term goal of this project is to elucidate design principles and paradigms that govern rapid tip growth to produce cells with extraordinary lengths. Rapid tip growth is essential for many cells to efficiently explore their environment or to reach their long-distance destination, e.g., fungal mycelia invades host cells or forage the environment, pollen tubes (PT) travel through female tissues to deliver sperms, and neuronal cells are targeted to their destination for unilateral signal propagation. Rapid tip growth requires efficient and targeted fusion of vesicles (containing cell membrane and wall materials) to the cell apex. This targeted exocytosis is highly coordinated in space and time and is orchestrated by a Rho GTPase-based signaling machinery localized to the cell tip. Little is known about how the signaling machinery is spatially and temporally coordinated at the rapidly expanding tip and how the tip-targeted exocytosis contributes to rapid tip growth. To address these questions, the principal investigator's group has established the Arabidopsis PT as a model system. Using this system, the principal investigator's group was the first to demonstrate the tip localization of a Rho GTPase and its essential role in a rapidly tip-growing cell. They uncover a tip-localized ROP1 signaling network and demonstrate that this network modulates tip-targeted exocytosis and self-regulates ROP1 in a manner dependent upon tip-localized actin microfilaments. Their genetic studies reveal a global mechanism for restricting ROP1 signaling to the tip, which involves exocytosis-based tip targeting of the REN1 RhoGAP that inactivates ROP1. The objective of this project is to test the hypothesis that ROP1-dependent exocytosis orchestrates the self-organizing rapid tip growth via multiple regulatory roles including the positive and negative feedback-based spatiotemporal coordination of the growth-signaling machinery and the modulation of the cell wall mechanics required for turgor-driven growth in PT. Aim 1 focuses on investigating the role of ROP1-dependent exocytosis in the feedback activation of ROP1 through its targeting of a cell surface receptor and its extracellular ligand that activate ROP1. Aim 2 will elucidate the mechanism behind the feedback inhibition of ROP1 by analyzing how exocytosis-mediated REN1 targeting coordinates with exocytosis-independent REN1 activation at the tip. Aim 3 will determine how ROP1-dependent exocytosis coordinates with clathrin-dependent endocytosis to modulate the cell wall mechanics necessary for sustained tip expansion. This work will provide a comprehensive view of the molecular and cellular mechanisms that control rapid tip growth in PT and will establish new paradigms and design principles for this fundamental process. Given the conserved Rho signaling underlying this process in diverse systems, these paradigms and principles will most likely enlighten mechanistic studies of similar processes in other medically relevant systems such as the invasive hyphal growth by pathogenic fungi. Therefore, the proposed research might ultimately be relevant to human health improvements.

描述（由申请人提供）：该项目的长期目标是阐明控制尖端快速生长以产生具有非凡长度的细胞的设计原理和范例。尖端的快速生长对于许多细胞有效地探索其环境或到达其远距离目的地至关重要，例如，真菌菌丝体侵入宿主细胞或在环境中寻找食物，花粉管（PT）穿过雌性组织传递精子，以及神经元细胞被定向到单边信号传播的目的地。尖端的快速生长需要囊泡（包含细胞膜和壁材料）与细胞顶端的有效和有针对性的融合。这种靶向胞吐作用在空间和时间上高度协调，并由位于细胞尖端的基于 Rho GTPase 的信号机制精心策划。关于信号机制如何在快速扩张的尖端进行空间和时间协调以及尖端靶向胞吐作用如何促进尖端快速生长，人们知之甚少。为了解决这些问题，主要研究小组建立了拟南芥 PT 作为模型系统。使用该系统，首席研究员的团队首次证明了 Rho GTPase 的尖端定位及其在快速尖端生长细胞中的重要作用。他们发现了尖端定位的 ROP1 信号网络，并证明该网络可以调节尖端靶向的胞吐作用，并以依赖于尖端定位的肌动蛋白微丝的方式自我调节 ROP1。他们的遗传学研究揭示了一种限制 ROP1 信号传导至尖端的全局机制，其中涉及基于胞吐作用的尖端靶向 REN1 RhoGAP，从而使 ROP1 失活。该项目的目的是检验 ROP1 依赖性胞吐作用通过多种调节作用协调自组织快速尖端生长的假设，包括基于正反馈和负反馈的生长信号机制的时空协调和细胞壁的调节PT 膨胀驱动生长所需的力学。目标 1 重点研究 ROP1 依赖性胞吐作用通过靶向细胞表面受体及其激活 ROP1 的胞外配体，在 ROP1 反馈激活中的作用。目标 2 将通过分析胞吐作用介导的 REN1 靶向如何与尖端的胞吐作用无关的 REN1 激活相协调，阐明 ROP1 反馈抑制背后的机制。目标 3 将确定 ROP1 依赖性胞吐作用如何与网格蛋白依赖性内吞作用协调，以调节持续尖端扩张所需的细胞壁力学。这项工作将提供控制 PT 尖端快速生长的分子和细胞机制的全面视图，并将为这一基本过程建立新的范例和设计原则。鉴于不同系统中这一过程中保守的 Rho 信号传导，这些范式和原理很可能会启发其他医学相关系统中类似过程的机制研究，例如病原真菌的侵入性菌丝生长。因此，拟议的研究最终可能与人类健康的改善相关。