骨骼肌中肌浆网/内质网钙ATP酶的功能及其作用机制

The Roles and Mechanisms of SERCA in Skeletal Muscle

骨骼肌是机体生命活动和能量代谢的重要场所,其代谢紊乱会诱发一系列肌肉疾病。Ca^(2+)作为肌肉收缩过程的重要调节器,在骨骼肌的功能行使中发挥重要作用。骨骼肌细胞中Ca^(2+)浓度主要受肌浆网/内质网钙ATP酶(sarcoplasmic/endoplasmic reticulum Ca^(2+)ATPase,SERCA)的调节。SERCA利用ATP水解产生的能量介导胞质Ca^(2+)进入肌浆网内腔,维持胞质Ca^(2+)平衡。SERCA功能的失调会引发一系列骨骼肌疾病,而SERCA活性受部分肌浆网蛋白质的调控,跨膜蛋白质PLN、SLN、MRLN、DWORF和sAnk1以及胞质蛋白质THADA和SAR,其通过磷酸化,进而调控SERCA的功能。本文对骨骼肌中SERCA的功能、调控SERCA的相关功能蛋白质的结构及其作用机制进行了总结,以期为骨骼肌相关疾病的治疗提供最新的思路和方法。

Skeletal muscle is an important organ for development and metabolism and its metabolic disorders will induce a series of muscle diseases.As an important regulator of the muscle contraction process,Ca^(2+)exerts a crucial role in regulating exercise performance of skeletal muscle.The concentration of Ca^(2+)in skeletal muscle cells is mainly regulated by sarcoplasmic/endoplasmic reticulum Ca^(2+)-ATPase(SERCA).SERCA mediates the passage of cytoplasmic Ca^(2+)into the lumen of sarcoplasmic reticulum supported by the energy generated from ATP hydrolysis,to maintain cytoplasmic Ca^(2+)balance.Dysfunction of SERCA triggers a series of skeletal muscle diseases.SERCA activity is regulated by some sarcoplasmic reticulum proteins,such as transmembrane proteins PLN,SLN,MRLN,DWORF and sAnk1,and the cytoplasmic proteins THADA and SAR,which regulate the function of SERCA through phosphorylation.In this paper,the functions of SERCA in skeletal muscle,the structures of related functional proteins that regulate SERCA and their mechanisms of action are summarized.This study will provide the latest ideas and methods for the clinical treatment on skeletal muscle diseases.