Pre-assembled Ca2+ entry units and constitutively active Ca2+ entry in skeletal muscle of calsequestrin-1 knockout mice.
Pre-assembled Ca2+ entry units and constitutively active Ca2+ entry in skeletal muscle of calsequestrin-1 knockout mice.
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DOI：
10.1085/jgp.202012617
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发表时间：
2020-10-05
期刊：
影响因子：
--
通讯作者：
Dirksen RT
中科院分区：
文献类型：
--
作者：
Michelucci A;Boncompagni S;Pietrangelo L;Takano T;Protasi F;Dirksen RT
Mice lacking calsequestrin-1 have reduced levels of releasable Ca2+ in the sarcoplasmic reticulum of their skeletal muscles. Michelucci et al. reveal that this is compensated by constitutive assembly of STIM1 and Orai1 into Ca2+ entry units, promoting both constitutive and store-operated Ca2+ entry. Store-operated Ca2+ entry (SOCE) is a ubiquitous Ca2+ influx mechanism triggered by depletion of Ca2+ stores from the endoplasmic/sarcoplasmic reticulum (ER/SR). We recently reported that acute exercise in WT mice drives the formation of Ca2+ entry units (CEUs), intracellular junctions that contain STIM1 and Orai1, the two key proteins mediating SOCE. The presence of CEUs correlates with increased constitutive- and store-operated Ca2+ entry, as well as sustained Ca2+ release and force generation during repetitive stimulation. Skeletal muscle from mice lacking calsequestrin-1 (CASQ1-null), the primary Ca2+-binding protein in the lumen of SR terminal cisternae, exhibits significantly reduced total Ca2+ store content and marked SR Ca2+ depletion during high-frequency stimulation. Here, we report that CEUs are constitutively assembled in extensor digitorum longus (EDL) and flexor digitorum brevis (FDB) muscles of sedentary CASQ1-null mice. The higher density of CEUs in EDL (39.6 ± 2.1/100 µm2 versus 2.0 ± 0.3/100 µm2) and FDB (16.7 ± 1.0/100 µm2 versus 2.7 ± 0.5/100 µm2) muscles of CASQ1-null compared with WT mice correlated with enhanced constitutive- and store-operated Ca2+ entry and increased expression of STIM1, Orai1, and SERCA. The higher ability to recover Ca2+ ions via SOCE in CASQ1-null muscle served to promote enhanced maintenance of peak Ca2+ transient amplitude, increased dependence of luminal SR Ca2+ replenishment on BTP-2-sensitive SOCE, and increased maintenance of contractile force during repetitive, high-frequency stimulation. Together, these data suggest that muscles from CASQ1-null mice compensate for the lack of CASQ1 and reduction in total releasable SR Ca2+ content by assembling CEUs to promote constitutive and store-operated Ca2+ entry.
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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：
5.5
作者：
Lyfenko, Alla D.;Dirksen, Robert T.
通讯作者：
Dirksen, Robert T.
影响因子：
5.5
作者：
Kurebayashi, N;Ogawa, Y
通讯作者：
Ogawa, Y
DOI：
10.1073/pnas.1009168108
发表时间：
2010-12-21
影响因子：
11.1
作者：
Canato, M.;Scorzeto, M.;Stienen, G. J. M.
通讯作者：
Stienen, G. J. M.
影响因子：
3.8
作者：
Loy, Ryan E.;Orynbayev, Murat;Dirksen, Robert T.
通讯作者：
Dirksen, Robert T.