Calcium coding mechanisms in plant cell growth and immunity

植物细胞生长和免疫中的钙编码机制

• 批准号: 10026845
• 负责人: Sheng Luan
• 金额: $ 34.21万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10026845
• 关键词: Address; Affect; Alzheimer' s Disease; Angiosperms; Animal Structures; Animals; Arabidopsis; Back; Binding; Biochemical; Biological Assay; Biological Models; Ca(2+)-Transporting ATPase; Calcium; Calcium Channel; Calcium Oscillations; Calcium Signaling; Calcium Spikes; Calmodulin; Cell membrane; Cells; Code; Complement; Complex; Coupling; Cyclic AMP; Cyclic GMP; Cyclic Nucleotides; Cytosol; Defect; Electrophysiology (science); Eukaryota; Female; Fertilization; Genetic; Growth; Health; Heart failure; Human; Hyphae; Image; Immune System Diseases; Immune response; Immunity; Knowledge; Laboratories; Laboratory Study; Link; Malignant Neoplasms; Medical; Metabolic Diseases; Modeling; Names; Natural Immunity; Neurodegenerative Disorders; Nucleotides; Pathway interactions; Peptide Receptor; Peptide Signal Sequences; Peptides; Phenotype; Phosphotransferases; Plants; Play; Pollen Tube; Process; Proteins; Protons; Regulation; Research; Role; Saccharomycetales; Second Messenger Systems; Sequence Analysis; Shapes; Signal Transduction; Specificity; Structure; Structure-Activity Relationship; Testing; Translating; Whole Organism; Work; autocrine; axon guidance; base; cell growth; cyclic-nucleotide gated ion channels; directional cell; genetic analysis; human disease; male; mutant; pathogenic bacteria; peptide hormone; polarized cell; receptor; reconstitution; response; sensor; sperm cell; tool; yeast genetics

Calcium (Ca) is a second messenger in all eukaryotes. Defects in Ca signaling cause numerous human diseases including Alzheimer’s disease, heart failure, metabolic diseases, immune disorders, neurodegenerative diseases, and cancer. Despite the importance and broad medical implications, Ca signaling mechanisms remain unclear. The challenging question concerns how Ca encodes specific information coming from different primary signals and translate them into distinct cellular responses. Coding and decoding the specificity of Ca signals remains a long-standing puzzle in the signal transduction field. The PI’s laboratory studies Ca coding and decoding mechanisms using Arabidopsis as a model system and has made breakthroughs in dissecting Ca- coding mechanisms, setting the stage for this application. The proposed studies seek to understand Ca-coding mechanisms in the contexts of pollen tube growth and innate immunity both of which involve cyclic nucleotide- gated channels (CNGCs) in Arabidopsis. The Specific Aim 1 will address the relationship between CNGC-based Ca oscillations and peptide signaling during pollen tube growth. PI’s lab identified two CNGC-type proteins and calmodulin (CaM) forming a Ca “oscillator” in pollen tube growth that also requires autocrine peptide hormones produced by pollen tube. The overarching hypothesis is that peptides bind to their receptors that in turn modulate Ca-oscillator channels. This will be tested through genetic analysis combined with single cell Ca imaging. The Specific Aim 2 will identify Ca transporters that work together with CNGCs in immunity signaling. The importance of Ca signaling has long been recognized in innate immunity for both animal and plant cells. PI’s lab identified a CNGC-type channel that generates cytoplasmic Ca spike in response to bacterial pathogens. Using genetic analysis in Arabidopsis and yeast genetic complementation models, Aim 2 will identify the transporters responsible for removing the Ca signal and study how they coordinate with CNGC-type channels to precisely shape the spatial and temporal dynamics of Ca codes. Specific Aim 3 seeks to understand the mechanisms for activation and inactivation of plant CNGCs. The CNGC-type channels function in both pollen tube and immunity models, but they consist of different subunits and their regulations by CaM are different too. Further, while animal CNGCs are activated by the cyclic nucleotides (cAMP/cGMP), the plant CNGCs in pollen tube and immunity models are insensitive to these nucleotides. The hypothesis is that plant CNGCs are regulated differently from animal counterparts and CaM-based regulation depends on subunit composition of the CNGCs. This hypothesis will be tested in Aim 3 using biochemical and electrophysiological approaches in both pollen tube and immunity model. Arabidopsis is an ideal model to address basic Ca signaling mechanisms, as it provides a plethora of genetic tools and an array of whole-organism and single-cell Ca signaling phenotypes in the genetic mutants. Completion of these aims will reveal new Ca coding mechanisms, contributing to the conceptual framework of Ca signaling highly relevant to human health.

钙（Ca）是所有真核生物中的第二信使。 Ca 信号传导缺陷导致多种人类疾病 包括阿尔茨海默病、心力衰竭、代谢疾病、免疫疾病、神经退行性疾病 疾病和癌症。尽管具有重要性和广泛的医学意义，Ca 信号传导机制仍然存在 不清楚。具有挑战性的问题涉及 Ca 如何编码来自不同初级的特定信息 信号并将其转化为不同的细胞反应。 Ca 信号特异性的编码和解码 仍然是信号转导领域长期存在的难题。 PI 的实验室研究 Ca 编码和 使用拟南芥作为模型系统的解码机制，并在解剖 Ca- 方面取得了突破 编码机制，为该应用程序奠定了基础。拟议的研究旨在了解 Ca 编码 花粉管生长和先天免疫背景下的机制都涉及环核苷酸- 拟南芥中的门控通道（CNGC）。具体目标 1 将解决基于 CNGC 的关系 花粉管生长过程中的 Ca 振荡和肽信号传导。 PI 的实验室鉴定出两种 CNGC 型蛋白质 钙调蛋白 (CaM) 在花粉管生长过程中形成 Ca“振荡器”，也需要自分泌肽激素 由花粉管产生。最重要的假设是肽与其受体结合，进而调节 Ca 振荡器通道。这将通过遗传分析结合单细胞 Ca 成像进行测试。这 具体目标 2 将鉴定在免疫信号传导中与 CNGC 协同工作的 Ca 转运蛋白。重要性 Ca 信号传导长期以来在动物和植物细胞的先天免疫中得到了认可。 PI 的实验室确定了 CNGC 型通道，可响应细菌病原体而产生细胞质 Ca 尖峰。利用遗传 在拟南芥和酵母遗传互补模型中进行分析，目标 2 将识别转运蛋白 负责去除 Ca 信号并研究它们如何与 CNGC 型通道协调以精确地 塑造 Ca 代码的空间和时间动态。具体目标 3 旨在了解 植物 CNGC 的活化和失活。 CNGC型通道在花粉管和免疫中发挥作用 模型，但它们由不同的子单元组成，并且 CaM 对它们的规定也不同。此外，虽然动物 CNGCs被环核苷酸(cAMP/cGMP)、花粉管中的植物CNGCs和免疫激活 模型对这些核苷酸不敏感。假设植物 CNGC 的调控方式与 动物对应物和基于 CaM 的调节取决于 CNGC 的亚基组成。这个假设 将在目标 3 中使用生化和电生理学方法对花粉管和免疫进行测试 模型。拟南芥是解决基本 Ca 信号传导机制的理想模型，因为它提供了大量的 遗传工具以及基因突变体中一系列整个生物体和单细胞 Ca 信号传导表型。 完成这些目标将揭示新的 Ca 编码机制，有助于构建 Ca 信号传导与人类健康高度相关。