Constitutive assembly of Ca2+ entry units in soleus muscle from calsequestrin knockout mice.
Constitutive assembly of Ca2+ entry units in soleus muscle from calsequestrin knockout mice.
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DOI：
10.1085/jgp.202213114
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发表时间：
2022-12-05
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影响因子：
--
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中科院分区：
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在比目鱼肌肌纤维中的Ca 2+进入单位的组装强烈依赖于钙螯合蛋白的表达，并与重复高频刺激和Orai 1表达期间增强的力产生相关，与提供Ca 2+流入源的连接一致。钙离子进入单位（Ca 2 + entry units，CEU）是肌节I带内肌浆网池与横小管延伸之间的连接点。CEU含有STIM 1和Orai 1蛋白，这是钙库操纵的钙离子进入（SOCE）的分子机制。在野生型（WT）小鼠趾长伸肌（EDL）纤维中，CEU在急性运动期间短暂组装，并在几小时后解体。相比之下，钙螯合蛋白-1（CASQ 1）消融诱导了EDL纤维中CEU的代偿性组成性组装，导致增强的组成性和最大SOCE，从而抵消了重复活动期间SR Ca 2+的耗尽。然而，CEU是否在表达骨骼CASQ 1和心脏CASQ 2亚型的慢缩纤维中形成尚不清楚。在此，我们比较了来自WT和敲除小鼠的比目鱼肌肌肉的结构和功能，这些小鼠缺乏CASQ 1（CASQ 1-null）或两种CASQs（dCASQ-null）。超微结构分析表明，SR/T-小管连接在I带，几乎相同的CEU在EDL肌肉，存在和更频繁的CASQ 1空比WT小鼠，与dCASQ-null表现出最高的发病率。来自dCASQ-null小鼠的比目鱼肌中CEU的更大发生率与重复高频刺激期间比力产生的增加相关，这取决于Ca 2+进入。与此一致，Orai 1表达在CASQ 1-null小鼠的比目鱼肌中显著增加，但与WT相比，在dCASQ-null小鼠中甚至更多。总之，这些结果强化了CEU组装强烈依赖于CASQ表达的概念，并提供了补充SR Ca 2+商店以维持持续肌肉活动期间特定力产生所需的Ca 2+的替代来源。
The assembly of Ca2+ entry units in soleus muscle fibers depends strongly on calsequestrin expression and correlates with both enhanced force production during repetitive high-frequency stimulation and Orai1 expression, consistent with junctions providing a source of Ca2+ influx. Calcium (Ca2+) entry units (CEUs) are junctions within the I band of the sarcomere between stacks of sarcoplasmic reticulum (SR) cisternae and extensions of the transverse (T)-tubule. CEUs contain STIM1 and Orai1 proteins, the molecular machinery of store-operated Ca2+ entry (SOCE). In extensor digitorum longus (EDL) fibers of wild-type (WT) mice, CEUs transiently assemble during acute exercise and disassemble several hours thereafter. By contrast, calsequestrin-1 (CASQ1) ablation induces a compensatory constitutive assembly of CEUs in EDL fibers, resulting in enhanced constitutive and maximum SOCE that counteracts SR Ca2+ depletion during repetitive activity. However, whether CEUs form in slow-twitch fibers, which express both the skeletal CASQ1 and the cardiac CASQ2 isoforms, is unknown. Herein, we compared the structure and function of soleus muscles from WT and knockout mice that lack either CASQ1 (CASQ1-null) or both CASQs (dCASQ-null). Ultrastructural analyses showed that SR/T-tubule junctions at the I band, virtually identical to CEUs in EDL muscle, were present and more frequent in CASQ1-null than WT mice, with dCASQ-null exhibiting the highest incidence. The greater incidence of CEUs in soleus from dCASQ-null mice correlated with increased specific force production during repetitive, high-frequency stimulation, which depended on Ca2+ entry. Consistent with this, Orai1 expression was significantly increased in soleus of CASQ1-null mice, but even more in dCASQ-null mice, compared with WT. Together, these results strengthen the concept that CEU assembly strongly depends on CASQ expression and provides an alternative source of Ca2+ needed to refill SR Ca2+ stores to maintain specific force production during sustained muscle activity.
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影响因子：
4.6
作者：
Boncompagni S;Michelucci A;Pietrangelo L;Dirksen RT;Protasi F
通讯作者：
Protasi F
影响因子：
7.8
作者：
EISENBERG, BR;KUDA, AM;PETER, JB
通讯作者：
PETER, JB
DOI：
10.1073/pnas.1101664108
发表时间：
2011-08-09
影响因子：
11.1
作者：
Hoover, Paul J.;Lewis, Richard S.
通讯作者：
Lewis, Richard S.
影响因子：
5.5
作者：
Cully, Tanya R.;Edwards, Joshua N.;Launikonis, Bradley S.
通讯作者：
Launikonis, Bradley S.
影响因子：
5.5
作者：
Kurebayashi, N;Ogawa, Y
通讯作者：
Ogawa, Y