Elucidation of MURC-mediated mechanisms of caveolae function and transportsome formation in cardiomyocytes

阐明 MURC 介导的心肌细胞小窝功能和转运体形成机制

• 批准号: 23591088
• 负责人: UEYAMA Tomomi
• 金额: $ 3.33万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591088/
• 关键词: 心肥大; カベオラ; 心筋細胞; MURC; cavin family

Immunoelectron microscopy revealed that MURC was expressed in caveolae and T tubules in cardiomyocytes, and transmission electron microscopy showed that caveolae were retained in cardiomyocytes of MURC-knockout (KO) mice. Alpha-1 adrenergic receptor (AR) stimulation-induced ERK activation and cardiac hypertrophy were attenuated in MURC-KO mice compared with wild-type mice. Upon alpha-1-AR stimulation, both MURC and phosphorylated ERK were translocated from the plasma membrane to the perinuclear region in cardiomyocytes. Immunoprecipitation revealed that MURC was associated with phosphorylated and total ERK. These findings suggest that MURC is dispensable for caveolar formation in cardiomyocytes, and that MURC serves as an ERK-recruiting protein in the caveolae within cardiomyocytes. The recruiting function of MURC is necessary to elicit efficient signaling of the alpha-1-AR/ERK cascade in the caveolae in cardiac hypertrophy.

免疫电镜显示MURC在心肌细胞的小窝和T小管中表达，透射电镜显示MURC敲除（KO）小鼠的心肌细胞中保留有小窝。与野生型小鼠相比，MURC-KO 小鼠中 Alpha-1 肾上腺素能受体 (AR) 刺激诱导的 ERK 激活和心脏肥大减弱。在 α-1-AR 刺激下，MURC 和磷酸化 ERK 均从心肌细胞的质膜转移至核周区域。免疫沉淀显示 MURC 与磷酸化和总 ERK 相关。这些发现表明，MURC 对于心肌细胞内小窝的形成是可有可无的，并且 MURC 在心肌细胞内的小窝中充当 ERK 募集蛋白。 MURC 的募集功能对于在心脏肥大的小窝中引发 α-1-AR/ERK 级联的有效信号传导是必要的。

项目成果

Genetic deletion of MURC/Cavin-4 aggravates abdominal aortic aneurysm

MURC/Cavin-4基因缺失加重腹主动脉瘤

• 发表时间: 2014
• 作者: Miyagawa K;Ogata T;Nakanishi N;Hamaoka T;Maruyama N;Ueyama T
• 通讯作者: Ueyama T

筋特異的カベオラ蛋白MURCはCaveolin-1とGα13-GTPの結合を競合阻害し、Rho/ROCK pathwayを介した肺血管平滑筋細胞の増殖能・遊走能を亢進させる

肌肉特异性小窝蛋白 MURC 竞争性抑制 Caveolin-1 和 Gα13-GTP 的结合，并通过 Rho/ROCK 途径增强肺血管平滑肌细胞的增殖和迁移能力。

• 发表时间: 2012
• 作者: 中西直彦;小形岳寛;宮川浩太郎;内藤大督;谷口琢也;沢田尚久;上山知己;松原弘明
• 通讯作者: 松原弘明

MURC/Cavin-4 has a protective role in the progression of abdominal aortic aneurysm

MURC/Cavin-4在腹主动脉瘤的进展中具有保护作用

• 发表时间: 2013
• 作者: Miyagawa K;Ogata T;Nakanishi N;Hamaoka T;Maruyama N;Ueyama T
• 通讯作者: Ueyama T

MURC functions as a caveolar scaffold protein for Rho signaling that regulates proliferation and migration of vascular smooth muscle cells

MURC 作为 Rho 信号的细胞膜穴支架蛋白发挥作用，调节血管平滑肌细胞的增殖和迁移

• 发表时间: 2012
• 作者: Nakanishi N;Ogata T;Miyagawa K;Naito D;Taniguchi T;Amano K;Ueyama T;Matsubara H
• 通讯作者: Matsubara H

MURC/Cavin-4 modulates caveolin-3 function and regulates cardiac function

MURC/Cavin-4 调节 Caveolin-3 功能并调节心脏功能

• 发表时间: 2014
• 作者: Hamaoka T;Naito D;Ogata T;Nakanishi N;Miyagawa K;Maruyama N;T Shirayama;Ueyama T
• 通讯作者: Ueyama T