Mechanisms by which phosphorylation and protein partners regulate Cx45

磷酸化和蛋白质伴侣调节 Cx45 的机制

基本信息

  • 批准号:
    10013271
  • 负责人:
  • 金额:
    $ 41.15万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-09-10 至 2023-06-30
  • 项目状态:
    已结题

项目摘要

Connexins are integral membrane proteins that oligomerize to form gap junction channels. Gap junctions composed of Cx43 mediate electrical coupling and impulse propagation in the normal working myocardium. In the failing heart, Cx43 remodeling (decreased expression, loss at intercalated discs, increased presence at lateral membranes) contributes to ventricular arrhythmias. However, the failing heart also aberrantly upregulates expression of Cx45 in ventricles, where it is normally at very low levels. This greatly enhances the propensity for arrhythmias, logically due to the low conductance and high voltage-sensitivity of Cx45 channels relative to Cx43. Crucially, the deleterious effect of Cx45 at the intercalated discs is likely amplified by the propensity of Cx45 to form heteromeric channels with Cx43, in which it has a dominant effect on the function of the resulting channels. Unfortunately, little is known about the mechanisms that drive Cx45 presence at intercalated discs or about the determinants of the functional properties of Cx45 that make its presence at ventricular intercalated discs dangerous. Studies proposed in Specific Aims 1 and 2 address novel mechanisms by which phosphorylation of the Cx45 carboxyl terminal (Cx45CT) domain modulates Cx45 protein partner interactions to increase or decrease gap junction intercellular communication in vitro and in vivo (and the differences from effects on Cx43). Specific Aim 3 focuses on determining how a recently discovered high-affinity protein-protein interaction of the Cx45CT, dimerization, affects the channel functional properties. The significance of this proposal is that discovery of how phosphorylations and interactions of the CT domain can be modulated would enable strategies to ameliorate pathological alterations of connexins the failing heart and elsewhere.
连接蛋白是完整的膜蛋白,寡聚形成间隙连接通道。差距

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 }}

Andrew L Harris其他文献

Andrew L Harris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('Andrew L Harris', 18)}}的其他基金

Mechanisms by which phosphorylation and protein partners regulate Cx45
磷酸化和蛋白质伴侣调节 Cx45 的机制
  • 批准号:
    10240634
  • 财政年份:
    2019
  • 资助金额:
    $ 41.15万
  • 项目类别:
Mechanisms by which phosphorylation and protein partners regulate Cx45
磷酸化和蛋白质伴侣调节 Cx45 的机制
  • 批准号:
    10434133
  • 财政年份:
    2019
  • 资助金额:
    $ 41.15万
  • 项目类别:
Development of a hepatoprotective strategy to prevent drug-induced liver injury
制定预防药物性肝损伤的保肝策略
  • 批准号:
    8592544
  • 财政年份:
    2013
  • 资助金额:
    $ 41.15万
  • 项目类别:
Development of a hepatoprotective strategy for preventing drug-induced liver inju
制定预防药物性肝损伤的保肝策略
  • 批准号:
    8723819
  • 财政年份:
    2013
  • 资助金额:
    $ 41.15万
  • 项目类别:
STRUCTURE-FUNCTION OF CONNEXIN PORES
连接蛋白孔的结构-功能
  • 批准号:
    7155886
  • 财政年份:
    2006
  • 资助金额:
    $ 41.15万
  • 项目类别:
STRUCTURE-FUNCTION OF CONNEXIN PORES
连接蛋白孔的结构-功能
  • 批准号:
    7236207
  • 财政年份:
    2006
  • 资助金额:
    $ 41.15万
  • 项目类别:
STRUCTURE-FUNCTION OF CONNEXIN PORES
连接蛋白孔的结构-功能
  • 批准号:
    7675278
  • 财政年份:
    2006
  • 资助金额:
    $ 41.15万
  • 项目类别:
STRUCTURE-FUNCTION OF CONNEXIN PORES
连接蛋白孔的结构-功能
  • 批准号:
    7477261
  • 财政年份:
    2006
  • 资助金额:
    $ 41.15万
  • 项目类别:
PROPERTIES OF CONNEXIN CHANNELS THAT CAUSE DEAFNESS
导致耳聋的连接蛋白通道的特性
  • 批准号:
    7018456
  • 财政年份:
    2005
  • 资助金额:
    $ 41.15万
  • 项目类别:
PROPERTIES OF CONNEXIN CHANNELS THAT CAUSE DEAFNESS
导致耳聋的连接蛋白通道的特性
  • 批准号:
    6904927
  • 财政年份:
    2005
  • 资助金额:
    $ 41.15万
  • 项目类别:

相似海外基金

How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 41.15万
  • 项目类别:
    Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 41.15万
  • 项目类别:
    Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 41.15万
  • 项目类别:
    Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 41.15万
  • 项目类别:
    Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 41.15万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 41.15万
  • 项目类别:
    Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 41.15万
  • 项目类别:
    Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 41.15万
  • 项目类别:
    Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
  • 批准号:
    23K00129
  • 财政年份:
    2023
  • 资助金额:
    $ 41.15万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
  • 批准号:
    2883985
  • 财政年份:
    2023
  • 资助金额:
    $ 41.15万
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了