STRUCTURE AND FUNCTION OF TITIN IN CARDIAC MYOFIBRILS

心肌原纤维中肌联蛋白的结构和功能

• 批准号: 3344511
• 负责人: MARION Lewis GREASER
• 金额: $ 6.34万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3344511
• 关键词: affinity chromatography; aging; chemical structure function; congestive heart failure; density gradient ultracentrifugation; gel electrophoresis; heart contraction; immunoelectron microscopy; immunofluorescence technique; monoclonal antibody; muscle proteins; myocardium; myocardium disorder; myofibrils; nonmammalian vertebrate embryology; sarcomeres; striated muscles; tissue /cell culture; tissue /cell preparation

The purpose of this study is to define the role ot titin in the structure and function of cardiac and skeletal muscle myofibrils. This protein, which has been reported to constitute as much as 10% of skeletal and 18% of cardiac myofibrils, has a subunit size in excess of 1,000,000 daltons. Studies are currently in progress to define the location of titin in the myofibril using monoclonal antibodies. Both fluorescence labeling on intact and partially extracted myofibrils and immunoelectron microscopic studies will be conducted. Attempts will be made to determine whether thick or thin filaments bind to isolated titin or whether other specific proteins (such as desmin, Alpha-actinin, myomesin, nebulin, etc.) may interact. Studies will be conducted to determine the relationship of titin appearance to myofibrillogenesis. The precise amount of titin in skeletal and cardiac myofibrils which have been purified on Percoll gradients will be analyzed. Changes in titin properties with age will be examined in normal and cardiomyopatihic hamster hearts. The elastic nature of titin and the apparent relationship between the high resting tension of cardiac muscle and the high titin content suggests it may play a key role in cardiac function. Changes and/or damage to titin may well be involved in the alterations occurring after a heart attack or in congestive heart failure.

本研究的目的是确定肌联蛋白在结构中的作用， 以及心肌和骨骼肌肌原纤维的功能。 这种蛋白质， 据报道，它构成了多达10%的骨骼和18%的 心肌肌原纤维的亚单位大小超过1，000，000道尔顿。 目前正在进行研究以确定肌联蛋白在细胞中的位置。 使用单克隆抗体的肌原纤维。 荧光标记 完整和部分提取的肌原纤维和免疫电镜 将进行研究。 将尝试确定是否 粗的或细的细丝与分离的肌联蛋白结合，或者其它特异性的 蛋白质（如结蛋白、α-辅肌动蛋白、肌溶蛋白、星云蛋白等）可以 互动. 将进行研究，以确定肌联蛋白的关系 肌原纤维发生的外观。 骨骼肌中肌联蛋白的精确含量 在Percoll梯度上纯化的心肌原纤维 被分析。 肌联蛋白性质随年龄的变化将在 正常和心肌病仓鼠心脏。 肌联蛋白的弹性性质 心肌静息张力增高与心肌缺血的关系 肌联蛋白的高含量表明它可能在 心脏功能 肌联蛋白的变化和/或损伤可能与 心脏病发作后或充血性心脏 失败

项目成果

Regulation of binding of subfragment 1 in isolated rigor myofibrils.

分离的僵硬肌原纤维中亚片段 1 结合的调节。

• DOI: 10.1083/jcb.111.6.2989
• 发表时间: 1990
• 期刊: The Journal of cell biology
• 作者: Swartz,DR;Greaser,ML;Marsh,BB
• 通讯作者: Marsh,BB

Partial titin cDNA sequence isolated from rabbit cardiac muscle RNA.

从兔心肌 RNA 中分离出部分肌联蛋白 cDNA 序列。

• DOI: 10.1007/bf00123100
• 发表时间: 1993
• 期刊: Journal of muscle research and cell motility
• 影响因子: 2.7
• 作者: Fritz,JD;Wolff,JA;Greaser,ML
• 通讯作者: Greaser,ML