Mitsugumin 53-mediated maintenance of K+ currents in cardiac myocytes.

Mitsugumin 53-mediated maintenance of K+ currents in cardiac myocytes.
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DOI:
10.4161/chan.3.1.7571
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发表时间:
2009-01
期刊:
Channels (Austin, Tex.)
影响因子:
--
通讯作者:
Takeshima H
Takeshima H
中科院分区:
其他
文献类型:
--
作者:
Masumiya H;Asaumi Y;Nishi M;Minamisawa S;Adachi-Akahane S;Yoshida M;Kangawa K;Ito K;Kagaya Y;Yanagisawa T;Yamazaki T;Ma J;Takeshima H

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Mitsugumin 53(MG53)是一个肌肉特异性的RBCC/TRIM家族成员,主要定位于质膜下的小泡上。在细胞表面损伤时,MG53以氧化依赖的方式将小泡招募到修复部位,MG53基因敲除的小鼠发展为与膜修复缺陷相关的进行性肌病。在这份报告中,我们关注的是MG53基因敲除的心肌细胞表现出异常的动作电位和K+电流密度降低。在培养细胞的cDNAi表达实验中,MG53可显著增加Kv2.1介导的电流,但不影响通道表达的总水平和细胞表面水平。在成像分析中,MG53似乎促进了含有Kv2.1的内吞囊泡在酸性pH下的运动。然而,在假定的显性-负性形式的MG53中,没有观察到类似的对电流密度和囊泡迁移率的影响。我们的数据表明,MG53参与了横纹肌中质膜和内体样囊泡之间的某些细胞表面蛋白的构成循环,也暗示了囊泡动力学对于心肌细胞Kv2.1的质量控制是必不可少的。
Mitsugumin 53 (MG53) is a muscle-specific RBCC/TRIM family member predominantly localized on small vesicles underneath the plasma membrane. Upon cell-surface lesion MG53 recruits the vesicles to the repair site in an oxidation-dependent manner and MG53-knockout mice develop progressive myopathy associated with defective membrane repair. In this report, we focus on MG53-knockout cardiomyocytes showing abnormal action potential profile and a reduced K+ current density. In cDNA expression experiments using cultured cells, KV2.1-mediated currents were remarkably increased by MG53 without affecting the total and cell-surface levels of channel expression. In imaging analysis MG53 seemed to facilitate the mobility of KV2.1-containing endocytic vesicles with acidic pH. However, similar effects on the current density and vesicular mobility were not observed in the putative dominant-negative form of MG53. Our data suggest that MG53 is involved in a constitutive cycle of certain cell-surface proteins between the plasma membrane and endosome-like vesicles in striated muscle, and also imply that the vesicular dynamics are essential for the quality control of KV2.1 in cardiomyocytes.
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