COLLABORATIVE RESEARCH: Development of the Triad Junction inSkeletal Muscle

合作研究：骨骼肌三联结的发展

• 批准号: 9206879
• 负责人: Mark Ellisman
• 金额: $ 9万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-01-01 至 1994-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9206879&HistoricalAwards=false
• 关键词: COLLABORATIVE; RESEARCH; Development; Triad; Junction

The triad junction is a complex structure involving plasma and sarcoplasmic reticulum membranes and at least seven proteins, and is the site where electrical excitation is transduced to release intracellular calcium, and thus has a critical role in coupling electrical excitation to muscle contraction. Additionally, it may interact with the cellular cytoskeleton to form muscle-specific morphology. Two key components of the triad junction, the dihydropyridine (DHPR) and ryanodine receptors (RR), are expressed early during embryonic chick skeletal muscle differentiation. The aim of this project is to determine how these proteins are incorporated into the triad junction and become active in the release of intracellular calcium in developing skeletal muscle, and whether the calcium release events mediated by the triad junction influence other aspects of muscle development. The specific aims are to: (1), define the experimental in detail by establishing the time course of the expression of the DHPR and RR in developing embryonic chick skeletal muscle; and (2), investigate whether these proteins influence skeletal muscle development by testing the hypothesis that DHPR and RR serve as organizers for the assembly of the triad junction and its integration into mature muscle structure. This will be done by defining the time course of incorporation of these and other junctional components into the junction, and assess the significance of interactions between junctional proteins and cytoskeletal elements. Dr. Ellisman's contribution to the project will be primarily with regard to the morphological aspects. Skeletal muscle provides the contractile force to move bones and other structures, effecting organ or whole organism movement. The signal which "tells" the muscle to contract and ensures synchronous contraction along the length of the muscle involves an electrical wave generated at the neuromuscular junction, which travels down the length of the muscle fiber along the plasma membrane. The conversion of the electrical signal to contraction occurs by transduction of the electrical signal to a "second messenger" signal, namely release of calcium from intracellular stores (sarcoplasmic reticulum) into the cytoplasm. At the "triad junction" of the muscle cell, the membrane of the sarcoplasmic reticulum is closely apposed to a specialized structure of the plasma membrane known as the transverse tubule. This highly specialized region contains a set of unique sarcoplasmic reticulum membrane proteins which interact with the closely apposed transverse tubule membrane to effect the coupling of the electrical signal to the opening of a calcium channel which allows the release of calcium from the sarcoplasmic reticulum to the cytoplasm. Neither the mechanism of this signal transduction event, nor the cellular development of this intricate subcellular structure, is well understood. The results of this research will increase our understanding of both of these very important processes in vertebrate muscle.

三元结是涉及等离子体的复杂结构， 肌浆网膜和至少七种蛋白质，和 是电刺激被转换释放的地方 细胞内钙，因此在偶联中具有关键作用 电刺激导致肌肉收缩。 此外，它可以 与细胞骨架相互作用形成肌肉特异性 形态学 三位一体交汇处的两个关键组成部分， 二氢吡啶（DHPR）和兰尼碱受体（RR），表达 在鸡胚骨骼肌分化早期。 的 该项目的目的是确定这些蛋白质是如何 融入了三位一体的交汇点，并成为活跃在 在发育中的骨骼肌中释放细胞内钙，和 是否由三联体连接介导的钙释放事件 影响肌肉发育的其他方面。 具体目标 （1）通过建立实验的详细定义， DHPR和RR在发育过程中表达的时程 鸡胚骨骼肌;（2），研究这些 蛋白质影响骨骼肌的发育， 假设DHPR和RR作为大会的组织者 三联体连接及其与成熟肌肉的整合 结构 这将通过定义以下时间过程来完成： 将这些和其它连接组件结合到 连接，并评估之间的相互作用的意义 连接蛋白和细胞骨架元件。 Ellisman博士 对该项目的贡献将主要是关于 形态学方面。 骨骼肌提供收缩力来移动骨骼， 其他结构，影响器官或整个有机体运动。 的 信号，“告诉”肌肉收缩，并确保同步 沿着肌肉长度的沿着收缩涉及电传导， 在神经肌肉接头处产生的波，向下传播 肌纤维沿质膜沿着的长度。 的 电信号到收缩的转换通过以下方式发生 将电信号转换为“第二信使” 信号，即从细胞内储存释放钙 （肌浆网）进入细胞质。 在“三合会 肌细胞的“连接”，肌浆细胞的膜 网织膜是密切并列的一个专门的结构， 质膜称为横小管。 这种高度 一个特殊的区域包含一套独特的肌浆网 膜蛋白与紧密并列的 横小管膜，以实现电耦合 信号的钙通道的开放，允许释放 从肌浆网到细胞质。 这种信号转导事件的机制， 这种复杂的亚细胞结构的细胞发育， 很好理解。 这项研究的结果将增加我们的 了解这两个非常重要的过程， 脊椎动物的肌肉