A new cytoplasmic interaction between junctin and ryanodine receptor Ca2+ release channels.
A new cytoplasmic interaction between junctin and ryanodine receptor Ca2+ release channels.
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DOI：
10.1242/jcs.160689
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发表时间：
2015-03-01
影响因子：
4
通讯作者：
Dulhunty AF
中科院分区：
文献类型：
--
作者：
Li L;Mirza S;Richardson SJ;Gallant EM;Thekkedam C;Pace SM;Zorzato F;Liu D;Beard NA;Dulhunty AF
连接蛋白是天冬氨酸-β-羟化酶（Asph）基因编码的一种非催化性剪接变体，插入肌浆网（SR）钙库的膜中，通过调节兰尼碱受体（RyR）钙释放通道来调节心脏和骨骼肌中的钙信号。连接蛋白是正常肌肉功能所必需的，因为其敲除导致异常Ca 2+信号传导、肌肉功能障碍和心律失常。然而，连接蛋白和RyRs之间的分子相互作用的性质在很大程度上是未知的，被认为是只发生在SR腔。我们发现，有大量的结合RyRs的完整的连接蛋白，和连接蛋白腔，出乎意料的是，细胞质结构域。这些不同的连接蛋白结构域的结合对RyR 1和RyR 2活性有不同的影响：在管腔溶液中的完整连接蛋白使RyR通道活性增加了1.53倍，C-末端管腔相互作用抑制了1.50%的RyR通道活性，N-末端细胞质结合使RyR活性增加了1.55倍。连接蛋白和RyR之间的细胞质相互作用是鲁米那结合所必需的，以复制完整连接蛋白对RyR 1和RyR 2活性的影响。连接蛋白的C-末端结构域与包括RyR 1的S1-S2接头的残基结合，连接蛋白的N-末端结构域与RyR 1残基1078和2156之间结合。
Junctin, a non-catalytic splice variant encoded by the aspartate-β-hydroxylase (Asph) gene, is inserted into the membrane of the sarcoplasmic reticulum (SR) Ca2+ store where it modifies Ca2+ signalling in the heart and skeletal muscle through its regulation of ryanodine receptor (RyR) Ca2+ release channels. Junctin is required for normal muscle function as its knockout leads to abnormal Ca2+ signalling, muscle dysfunction and cardiac arrhythmia. However, the nature of the molecular interaction between junctin and RyRs is largely unknown and was assumed to occur only in the SR lumen. We find that there is substantial binding of RyRs to full junctin, and the junctin luminal and, unexpectedly, cytoplasmic domains. Binding of these different junctin domains had distinct effects on RyR1 and RyR2 activity: full junctin in the luminal solution increased RyR channel activity by ∼threefold, the C-terminal luminal interaction inhibited RyR channel activity by ∼50%, and the N-terminal cytoplasmic binding produced an ∼fivefold increase in RyR activity. The cytoplasmic interaction between junctin and RyR is required for luminal binding to replicate the influence of full junctin on RyR1 and RyR2 activity. The C-terminal domain of junctin binds to residues including the S1–S2 linker of RyR1 and N-terminal domain of junctin binds between RyR1 residues 1078 and 2156.
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影响因子：
4.8
作者：
Groh, S;Marty, I;Ronjat, M
通讯作者：
Ronjat, M
影响因子：
3.7
作者：
Boncompagni, Simona;Thomas, Monique;Perez, Claudio F.
通讯作者：
Perez, Claudio F.
影响因子：
13.5
作者：
Györke S;Carnes C
通讯作者：
Carnes C
影响因子：
4.8
作者：
Jones, LR;Zhang, L;Kelley, J
通讯作者：
Kelley, J
DOI：
10.1083/jcb.99.3.875
发表时间：
1984-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Saito A;Seiler S;Chu A;Fleischer S
通讯作者：
Fleischer S