M-Line Proteins and A-Band Assembly in Skeletal Muscle

骨骼肌中的 M 线蛋白和 A 带组装

基本信息

项目摘要

Myofibrillogenesis is a highly complex process that depends on the coordinated assembly and integration of a number of contractile, cytoskeletal and signaling proteins into regular arrays, the sarcomeres. Myosin Binding Protein C (MyBP-C), a protein associated with thick filaments, is believed to have both a structural and a regulatory role within the muscle cell, by contributing to the normal assembly and stabilization of thick filaments and modulating the number of myosin heads available for involvement in the contractile cycle. Obscurin, a giant myofibrillar protein, that closely surrounds Z-disks and M-lines, interacts specifically and directly with a novel isoform of MyBP-C slow, MyBP-C(+) slow, that appears to selectively concentrate at the M-line. Consequently, we hypothesize that the binding of obscurin with MyBP-C(+) slow contributes to the assembly, stabilization and maintenance of sarcomeric myosin into regular A-bands, through formation of primitive M-lines that may serve as scaffolding structures. We propose to test this hypothesis through three specific aims: (I) to characterize the novel MyBP-C(+) slow isoform in differentiating and adult skeletal muscle fibers, using a wide array of molecular, cellular and immunological approaches; (II) to study the interaction between obscurin and MyBP-C(+) slow qualitatively, by in vitro and in vivo binding assays, and quantitatively, by surface plasmon resonance technology and (III) to investigate the physiological significance of the binding of obscurin to MyBP-C(+) slow in the assembly and organization of myosin thick filaments into periodic A-bands, using adenovirally-mediated gene transfer and small inhibitory RNA technology. Knowledge gained from the proposed studies will provide new insights into the molecular mechanisms that integrate thick filaments into sarcomeres of normal skeletal fibers and how they are compromised in human muscle disease.
肌原纤维发生是一个高度复杂的过程,依赖于肌原纤维的协调组装和整合。 许多收缩性的、细胞骨架的和信号蛋白形成规则的阵列,即肌节。肌球 结合蛋白C(MyBP-C),一种与粗丝相关的蛋白质,被认为具有两种结构, 以及在肌细胞内的调节作用,通过促进厚膜的正常组装和稳定, 丝和调节可用于参与收缩周期的肌球蛋白头的数量。 Obscurin是一种巨大的肌原纤维蛋白,紧密围绕Z盘和M线, 直接与MyBP-C慢亚型MyBP-C(+)慢亚型,似乎选择性地集中在 M线因此,我们假设obscurin与MyBP-C(+)的结合缓慢有助于MyBP-C(+)的表达。 肌节肌球蛋白的组装、稳定和维持为规则的A带, 可以用作脚手架结构的原始M线。我们建议通过三个方面来检验这一假设。 具体目的:(I)表征分化和成人骨骼肌中新的MyBP-C(+)慢亚型, 肌纤维,使用广泛的分子,细胞和免疫学方法;(II)研究 通过体外和体内结合测定,obscurin和MyBP-C(+)之间的相互作用定性地减慢, 定量,通过表面等离子体共振技术和(III)调查生理 Obscurin与MyBP-C(+)结合在肌球蛋白粗蛋白组装和组织中的意义 利用腺病毒介导的基因转移和小的抑制性RNA, 技术.从拟议的研究中获得的知识将为分子生物学提供新的见解。 将粗丝整合到正常骨骼纤维的肌节中的机制以及它们是如何 在人类肌肉疾病中受损。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Aikaterini Kontrogianni-Konstantopoulos其他文献

Aikaterini Kontrogianni-Konstantopoulos的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Aikaterini Kontrogianni-Konstantopoulos', 18)}}的其他基金

Obscurin-kinase 1/N-cadherin: a new signaling axis in cardiac structure/function
暗蛋白激酶 1/N-钙粘蛋白:心脏结构/功能中的新信号轴
  • 批准号:
    10532967
  • 财政年份:
    2022
  • 资助金额:
    $ 27.98万
  • 项目类别:
Obscurin-kinase 1/N-cadherin: a new signaling axis in cardiac structure/function
暗蛋白激酶 1/N-钙粘蛋白:心脏结构/功能中的新信号轴
  • 批准号:
    10677738
  • 财政年份:
    2022
  • 资助金额:
    $ 27.98万
  • 项目类别:
Novel MYBPC1 mutations cosegregate with a myopathy associated with muscle weakness, hypotonia and tremor
新型 MYBPC1 突变与肌无力、肌张力减退和震颤相关的肌病共分离
  • 批准号:
    10249220
  • 财政年份:
    2020
  • 资助金额:
    $ 27.98万
  • 项目类别:
Novel MYBPC1 mutations cosegregate with a myopathy associated with muscle weakness, hypotonia and tremor
新型 MYBPC1 突变与肌无力、肌张力减退和震颤相关的肌病共分离
  • 批准号:
    10693128
  • 财政年份:
    2020
  • 资助金额:
    $ 27.98万
  • 项目类别:
Novel MYBPC1 mutations cosegregate with a myopathy associated with muscle weakness, hypotonia and tremor
新型 MYBPC1 突变与肌无力、肌张力减退和震颤相关的肌病共分离
  • 批准号:
    10470181
  • 财政年份:
    2020
  • 资助金额:
    $ 27.98万
  • 项目类别:
Regulation of MyBP-C slow via phosphorylation in skeletal muscles
通过骨骼肌磷酸化缓慢调节 MyBP-C
  • 批准号:
    9769620
  • 财政年份:
    2018
  • 资助金额:
    $ 27.98万
  • 项目类别:
HAX-1: a Multifaceted Family of Apoptotic Regulators
HAX-1:多方面的凋亡调节因子家族
  • 批准号:
    8206608
  • 财政年份:
    2010
  • 资助金额:
    $ 27.98万
  • 项目类别:
HAX-1: a Multifaceted Family of Apoptotic Regulators
HAX-1:多方面的凋亡调节因子家族
  • 批准号:
    8030970
  • 财政年份:
    2010
  • 资助金额:
    $ 27.98万
  • 项目类别:
M-Line Proteins and A-Band Assembly in Skeletal Muscle
骨骼肌中的 M 线蛋白和 A 带组装
  • 批准号:
    7385086
  • 财政年份:
    2006
  • 资助金额:
    $ 27.98万
  • 项目类别:
M-Line Proteins and A-Band Assembly in Skeletal Muscle
骨骼肌中的 M 线蛋白和 A 带组装
  • 批准号:
    7215657
  • 财政年份:
    2006
  • 资助金额:
    $ 27.98万
  • 项目类别:

相似海外基金

Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
  • 批准号:
    MR/Z503605/1
  • 财政年份:
    2024
  • 资助金额:
    $ 27.98万
  • 项目类别:
    Research Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
  • 批准号:
    2402691
  • 财政年份:
    2024
  • 资助金额:
    $ 27.98万
  • 项目类别:
    Standard Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
  • 批准号:
    2336167
  • 财政年份:
    2024
  • 资助金额:
    $ 27.98万
  • 项目类别:
    Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
  • 批准号:
    24K12150
  • 财政年份:
    2024
  • 资助金额:
    $ 27.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
  • 批准号:
    2341428
  • 财政年份:
    2024
  • 资助金额:
    $ 27.98万
  • 项目类别:
    Standard Grant
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
  • 批准号:
    DE240100561
  • 财政年份:
    2024
  • 资助金额:
    $ 27.98万
  • 项目类别:
    Discovery Early Career Researcher Award
Laboratory testing and development of a new adult ankle splint
新型成人踝关节夹板的实验室测试和开发
  • 批准号:
    10065645
  • 财政年份:
    2023
  • 资助金额:
    $ 27.98万
  • 项目类别:
    Collaborative R&D
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
  • 批准号:
    23K09542
  • 财政年份:
    2023
  • 资助金额:
    $ 27.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
  • 批准号:
    23K07552
  • 财政年份:
    2023
  • 资助金额:
    $ 27.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
  • 批准号:
    23K07559
  • 财政年份:
    2023
  • 资助金额:
    $ 27.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了