Analysis of calcium signaling in C. elegans

线虫中钙信号传导的分析

• 批准号: 10363475
• 负责人: JOSHUA M KAPLAN
• 金额: $ 58.62万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10363475
• 关键词: Action Potentials; Address; Binding Proteins; Biology; Biophysics; CREB1 gene; Caenorhabditis elegans; Calcineurin; Calcium; Calcium Channel; Calcium Signaling; Calmodulin; Candidate Disease Gene; Cells; Coupled; Coupling; Defect; Endoplasmic Reticulum; Enzymes; Frequencies; Genes; Genetic; Genetic Transcription; Goals; HDAC4 gene; Histone Deacetylase; Homeostasis; Mediating; Membrane; Modeling; Molecular; Motor Neurons; Muscle; Muscle Contraction; Muscle function; Mutation; Neuromuscular Junction; Neurons; Neuropeptides; Neurotransmitters; Pathologic; Pattern; Phosphotransferases; Play; Potassium Channel; Presynaptic Terminals; Probability; Protein Kinase; Protein phosphatase; Receptor Activation; Role; Ryanodine Receptors; Signal Transduction; Source; Speed; Synapses; Synaptic Receptors; Testing; Time; cell type; experimental study; insight; large-conductance calcium-activated potassium channels; millisecond; muscle physiology; mutant; mutation screening; nanometer; nervous system disorder; neurotransmitter release; optogenetics; receptor coupling; recruit; response; synaptic function; transcription factor; voltage

Analysis of calcium signaling in C. elegans The goal of this project is to analyze mechanisms controlling signaling by voltage-activated calcium (CaV) channels. In neurons and muscles, brief cytoplasmic calcium transients efficiently and rapidly activate downstream effectors, often on millisecond time scales. One general mechanism that promotes signal speed and efficiency is tight spatial coupling between CaV channels and their effectors, which is termed calcium nanodomain signaling. We propose three Aims to study nanodomain signaling by CaV channels. First, we identify genes required to promote coupling of CaV1 (L-type) channels to two effectors, calcium activated BK potassium channels and ryanodine receptors (RYR), which are calcium release channels in the endoplasmic reticulum. Second, we test models for how the threshold is set for activity induced gene transcription, and if this threshold is shifted by mutations in specific calcium activated signaling components or by endogenous neuropeptides. Third, we ask how CaV1 and 2 channels are localized at presynaptic terminals, which dictates neurotransmitter release probability. These Aims address fundamental mechanisms controlling neuron and muscle physiology.

分析了C. elegans 这个项目的目标是分析控制信号的机制， 电压激活钙通道（CaV）。在神经元和肌肉中， 钙瞬变有效和迅速地激活下游效应器，通常在 毫秒时间尺度一种提高信号速度的通用机制， 效率是CaV通道与其效应子之间的紧密空间耦合， 称为钙纳米结构域信号传导。我们提出了三个研究纳米畴的目标 通过CaV通道进行信号传导。首先，我们确定了促进偶联所需的基因， CaV1（L型）通道与两种效应器，钙激活BK钾通道和 兰尼碱受体（Ryanodine receptor，RYR）是内质网中的钙释放通道， 网状细胞。其次，我们测试了如何为活性诱导基因设置阈值的模型， 转录，如果这一阈值是由特定的钙激活的突变转移， 信号传导成分或内源性神经肽。第三，我们问CaV 1和2如何 通道位于突触前末梢，决定神经递质的释放 概率这些目标解决了控制神经元的基本机制， 肌肉生理学