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个信使。 CA信号中的缺陷导致许多人类疾病 包括阿尔茨海默氏病，心力衰竭，代谢疾病，免疫疾病，神经退行性疾病 疾病和癌症。尽管重要性和广泛的医学意义，但CA信号传导机制仍然存在 不清楚。挑战问题涉及CA如何编码来自不同主要的特定信息 信号并将其转换为不同的细胞反应。编码和解码CA信号的特异性 在信号传输场中仍然是一个长期的难题。 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。拟议的研究试图了解CA编码 在花粉管生长和先天免疫组织派的背景下的机制，这两种机制都涉及环状核苷酸 - 拟南芥的门控通道（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的实验室确定了两种CNGC型蛋白质和 在花粉管生长中形成CA“振荡器”的钙调蛋白（CAM）也需要自分泌肽激素 由花粉管产生。总体假设是肽与其接收器结合，然后调节 CA振荡器通道。这将通过遗传分析与单细胞CA成像结合进行测试。这 特定的目标2将识别与免疫信号中CNGC一起工作的CA转运蛋白。重要性 长期以来，CA信号在动物和植物细胞的先天免疫力中已被识别。 PI的实验室确定了 CNGC型通道会对细菌病原体产生细胞质CA尖峰。使用通用 在拟南芥和酵母遗传完成模型中，AIM 2将识别转运蛋白 负责删除CA信号并研究它们如何与CNGC型通道协调至精确 塑造CA代码的空间和临时动力学。特定目标3试图了解 植物CNGC的激活和失活。 CNGC型通道在花粉管和免疫力中的功能 模型，但它们由不同的亚基组成，凸轮的法规也不同。此外，动物 CNGC被环状核苷酸（CAMP/CGMP），花粉管中的植物CNGC和免疫激活 模型对这些核苷酸不敏感。假设是，植物CNGC的调节与 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 将使用花粉管和免疫的生化和电生理方法在AIM 3中进行测试 模型。拟南芥是解决基本CA信号传导机制的理想模型，因为它提供了很多 基因突变体中的遗传工具以及一系列的全生物和单细胞CA信号表型。 这些目标的完成将揭示新的CA编码机制，从而有助于 CA信号与人类健康高度相关。