The regulation of SERCA-type pumps by phospholamban and sarcolipin
The regulation of SERCA-type pumps by phospholamban and sarcolipin
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DOI：
10.1111/j.1749-6632.2003.tb07231.x
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发表时间：
2003-01-01
期刊：
影响因子：
--
通讯作者：
Tupling, AR
中科院分区：
文献类型：
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作者：
MacLennan, DH;Asahi, M;Tupling, AR
肌磷脂（SLN）和受磷蛋白（PLN）都降低了SERCA 1a或SERCA 2a对Ca 2+的表观亲和力。由于SLN和PLN在心脏中共表达，因此研究了这三种蛋白质之间的相互作用。当SERCA 1a或SERCA 2a在HEK-293细胞中与SLN和PLN共表达时，产生超抑制。SLN提高PLN单体含量的能力至少部分地解释了SLN在PLN存在下的超抑制作用。为了评价SLN在骨骼肌中的作用，将SLN cDNA直接注射到大鼠比目鱼肌中并分析力特性。SLN的过度表达导致抽搐和强直峰值力幅度和最大收缩和舒张速率的显着降低，以及重复电刺激的疲劳性增加。肌浆Ca ~（2+）摄取受损，提示SLN过表达可减少肌浆网Ca ~（2+）库。SLN和PLN似乎与SERCA中相同的调节位点结合。然而，在三元复合物中，PLN占据调节位点，SLN结合PLN的暴露侧和SERCA。
Both sarcolipin (SLN) and phospholamban (PLN) lower the apparent affinity of either SERCA1a or SERCA2a for Ca2+. Since SLN and PLN are coexpressed in the heart, interactions among these three proteins were investigated. When SERCA1a or SERCA2a were coexpressed in HEK-293 cells with both SLN and PLN, superinhibition resulted. The ability of SLN to elevate the content of PLN monomers accounts, at least in part, for the superinhibitory effects of SLN in the presence of PLN. To evaluate the role of SLN in skeletal muscle, SLN cDNA was injected directly into rat soleus muscle and force characteristics were analyzed. Overexpression of SLN resulted in significant reductions in both twitch and tetanic peak force amplitude and maximal rates of contraction and relaxation and increased fatigability with repeated electrical stimulation. Ca2+ uptake in muscle homogenates was impaired, suggesting that overexpression of SLN may reduce the sarcoplasmic reticulum Ca2+ store. SLN and PLN appear to bind to the same regulatory site in SERCA. However, in a ternary complex, PLN occupies the regulatory site and SLN binds to the exposed side of PLN and to SERCA.