Triadin/Junctin Double Null Mouse Reveals a Differential Role for Triadin and Junctin in Anchoring CASQ to the jSR and Regulating Ca2+ Homeostasis
Triadin/Junctin Double Null Mouse Reveals a Differential Role for Triadin and Junctin in Anchoring CASQ to the jSR and Regulating Ca2+ Homeostasis
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DOI：
10.1371/journal.pone.0039962
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发表时间：
2012-07-02
期刊：
影响因子：
3.7
通讯作者：
Perez, Claudio F.
中科院分区：
文献类型：
--
作者：
Boncompagni, Simona;Thomas, Monique;Perez, Claudio F.
Triadin（Tdn）和Junctin（Jct）是结构相关的跨膜蛋白，被认为是钙螯合蛋白（CASQ）和连接肌浆网（jSR）处的兰尼碱受体（RyRs）之间的结构和功能相互作用的关键介质。然而，每种蛋白质对jSR结构和对兴奋-收缩（e-c）偶联的具体贡献尚未完全确定。在这里，使用缺乏Tdn（Tdn-null），Jct（Jct-null）或两者（Tdn/Jct-null）的小鼠模型，我们将Tdn确定为将CASQ连接到带有RyR的jSR膜的周期性定位锚的主要成分。这两种蛋白质被证明是重要的结构组织的jSR池和保留CASQ在其中，但有不同程度的影响。我们的研究结果还表明，CASQ的存在是负责宽腔的jSR池。使用Ca 2+成像和Ca 2+选择性微电极，我们发现，在e-c耦合，SR Ca 2+含量和静息[Ca 2 +]在Jct，Tdn和Tdn/Jct-null肌肉的变化直接相关的CASQ含量和其组织内的jSR的每一个删除的效果。这些数据表明，在骨骼肌中，Tdn/CASQ连接的中断对jSR结构和肌浆Ca 2+调节的影响比Jct/CASQ关联更深远。
Triadin (Tdn) and Junctin (Jct) are structurally related transmembrane proteins thought to be key mediators of structural and functional interactions between calsequestrin (CASQ) and ryanodine receptor (RyRs) at the junctional sarcoplasmic reticulum (jSR). However, the specific contribution of each protein to the jSR architecture and to excitation-contraction (e-c) coupling has not been fully established. Here, using mouse models lacking either Tdn (Tdn-null), Jct (Jct-null) or both (Tdn/Jct-null), we identify Tdn as the main component of periodically located anchors connecting CASQ to the RyR-bearing jSR membrane. Both proteins proved to be important for the structural organization of jSR cisternae and retention of CASQ within them, but with different degrees of impact. Our results also suggest that the presence of CASQ is responsible for the wide lumen of the jSR cisternae. Using Ca2+ imaging and Ca2+ selective microelectrodes we found that changes in e-c coupling, SR Ca2+ content and resting [Ca2+] in Jct, Tdn and Tdn/Jct-null muscles are directly correlated to the effect of each deletion on CASQ content and its organization within the jSR. These data suggest that in skeletal muscle the disruption of Tdn/CASQ link has a more profound effect on jSR architecture and myoplasmic Ca2+ regulation than Jct/CASQ association.