Periasamy Muthu, Maurya Santosh Kumar, Sahoo Sanjaya Kumar, Singh Sushant, Sahoo Sanjaya Kumar, Reis Felipe C G, Bal Naresh Chandra
Sanford Burnham Prebys Medical Discovery Institute at Lake Nona, Orlando , Florida, USA.
School of Biotechnology, KIIT University, Bhubaneswar, Odisha, India.
Compr Physiol. 2017 Jun 18;7(3):879-890. doi: 10.1002/cphy.c160030.
In muscle cells, the sarcoplasmic reticulum (SR) not only acts as a Ca2+ store, but also regulates the contractile characteristics of the muscle. Ca2+ release from the SR is the primary mechanism for activating muscle contraction and reuptake of Ca2+ by the sarcoplasmic reticulum Ca2+ ATPase (SERCA) pump causes muscle relaxation. The SERCA pump isoforms are encoded by three genes, SERCA 1, 2, and 3, which are differentially expressed in muscle and determine SR Ca2+ dynamics by affecting the rate and amount of Ca2+ uptake, thereby affecting SR store and release of Ca2+ in muscle. In muscle, small molecular weight proteins, including Phospholamban (PLB) and Sarcolipin (SLN), also regulate the SERCA pump. Regulation of the SERCA pump by PLB or SLN affects cytosolic Ca2+ dynamics and changes in cytosolic Ca2+ not only affect contractile function, but also mitochondrial ATP production. Recent studies have shown that alterations in cytosolic Ca2+ affects Ca2+ entry into mitochondria and ATP production; thus, Ca2+ serves as an integrating signal between muscle contraction-dependent energy demand and mitochondrial energy production. In addition, changes in cytosolic Ca2+ can affect Ca2+ signaling pathways modulating gene expression and muscle growth. An emerging area of research shows that SR Ca2+ cycling is also a player in muscle-based nonshivering thermogenesis. Recent data shows that SERCA uncoupling by SLN leads to increased ATP hydrolysis and heat production. Our studies, using genetically altered mouse models of SLN, show that SLN/SERCA interaction plays an important role in muscle thermogenesis and metabolism, which will be discussed here, in great length. © 2017 American Physiological Society. Compr Physiol 7:879-890, 2017.
在肌肉细胞中，肌浆网（SR）不仅作为钙离子的储存库，还调节肌肉的收缩特性。肌浆网释放钙离子是激活肌肉收缩的主要机制，而肌浆网钙离子ATP酶（SERCA）泵对钙离子的再摄取则导致肌肉舒张。SERCA泵同工型由SERCA 1、2和3这三个基因编码，它们在肌肉中差异表达，并通过影响钙离子摄取的速率和量来决定肌浆网钙离子动力学，从而影响肌肉中肌浆网钙离子的储存和释放。在肌肉中，包括受磷蛋白（PLB）和肌脂蛋白（SLN）在内的小分子蛋白也调节SERCA泵。PLB或SLN对SERCA泵的调节会影响胞质钙离子动力学，而胞质钙离子的变化不仅会影响收缩功能，还会影响线粒体ATP的产生。最近的研究表明，胞质钙离子的改变会影响钙离子进入线粒体以及ATP的产生；因此，钙离子作为肌肉收缩依赖性能量需求和线粒体能量产生之间的整合信号。此外，胞质钙离子的变化会影响调节基因表达和肌肉生长的钙离子信号通路。一个新兴的研究领域表明，肌浆网钙离子循环在基于肌肉的非寒战产热中也发挥作用。最近的数据表明，SLN导致的SERCA解偶联会增加ATP水解和热量产生。我们利用SLN基因改变的小鼠模型进行的研究表明，SLN/SERCA相互作用在肌肉产热和代谢中起重要作用，本文将对此进行详细讨论。© 2017美国生理学会。综合生理学7:879 - 890, 2017。
