Myofibrillar protein turnover: the proteasome and the calpains.
Myofibrillar protein turnover: the proteasome and the calpains.
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DOI：
10.2527/jas.2007-0395
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发表时间：
2008-04
影响因子：
3.3
通讯作者：
D. E. Goll;G. Neti;S. Mares;V. F. Thompson
中科院分区：
文献类型：
--
作者：
D. E. Goll;G. Neti;S. Mares;V. F. Thompson
骨骼肌中肌原纤维蛋白的代谢周转要求在降解为AA之前，肌原纤维蛋白从肌原纤维中除去，而不破坏肌原纤维收缩和产生张力的能力。骨骼肌含有4种蛋白水解系统，其量使得它们可能参与代谢蛋白质周转：1）溶酶体系统，2）半胱天冬酶系统，3）钙蛋白酶系统，和4）蛋白酶体。溶酶体中的组织蛋白酶在细胞质的中性pH下没有活性，因此如果涉及溶酶体系统，则肌原纤维蛋白必须在溶酶体内降解。溶酶体不能在不破坏肌原纤维的情况下吞噬肌原纤维，因此溶酶体系统在很大程度上不参与肌原纤维蛋白的代谢周转。半胱天冬酶直到细胞凋亡开始才被激活，因此，半胱天冬酶不太可能在肌原纤维蛋白质周转中参与到显著的程度。钙蛋白酶不将蛋白质降解为AA或甚至小肽，并且不催化肌浆蛋白的大量降解，因此它们不是参与肌原纤维蛋白周转的唯一蛋白水解系统。过去20年的研究表明，蛋白酶体负责细胞内总蛋白质周转的80%至90%，但蛋白酶体仅在肽链解折叠后降解肽链，以便它们可以进入蛋白酶体的催化室。因此，虽然蛋白酶体可以降解肌浆蛋白，但它不能降解肌原纤维蛋白，直到它们从肌原纤维中被去除。目前尚不清楚这种移除是如何完成的。钙蛋白酶降解那些参与保持肌原纤维蛋白组装在肌原纤维中的蛋白质，并且在30多年前提出钙蛋白酶通过从肌原纤维拆卸蛋白质外层并将其释放为肌丝来启动肌原纤维蛋白质周转。这样的肌丝已经在骨骼肌中发现。其他研究表明，个别肌原纤维蛋白可以与它们在细胞质中的对应物交换;目前还不清楚这是否可以在一定程度上与活肌肉中肌原纤维蛋白的周转率一致。钙蛋白酶和蛋白酶体似乎都参与了肌原纤维蛋白的更新，但其机制尚不清楚。
Metabolic turnover of myofibrillar proteins in skeletal muscle requires that, before being degraded to AA, myofibrillar proteins be removed from the myofibril without disrupting the ability of the myofibril to contract and develop tension. Skeletal muscle contains 4 proteolytic systems in amounts such that they could be involved in metabolic protein turnover: 1) the lysosomal system, 2) the caspase system, 3) the calpain system, and 4) the proteasome. The catheptic proteases in lysosomes are not active at the neutral pH of the cell cytoplasm, so myofibrillar proteins would have to be degraded inside lysosomes if the lysosomal system were involved. Lysosomes could not engulf a myofibril without destroying it, so the lysosomal system is not involved to a significant extent in metabolic turnover of myofibrillar proteins. The caspases are not activated until initiation of apoptosis, and, therefore, it is unlikely that the caspases are involved to a significant extent in myofibrillar protein turnover. The calpains do not degrade proteins to AA or even to small peptides and do not catalyze bulk degradation of the sarcoplasmic proteins, so they cannot be the only proteolytic system involved in myofibrillar protein turnover. Research during the past 20 yr has shown that the proteasome is responsible for 80 to 90% of total intracellular protein turnover, but the proteasome degrades peptide chains only after they have been unfolded, so that they can enter the catalytic chamber of the proteasome. Thus, although the proteasome can degrade sarcoplasmic proteins, it cannot degrade myofibrillar proteins until they have been removed from the myofibril. It remains unclear how this removal is done. The calpains degrade those proteins that are involved in keeping the myofibrillar proteins assembled in myofibrils, and it was proposed over 30 yr ago that the calpains initiated myofibrillar protein turnover by disassembling the outer layer of proteins from the myofibril and releasing them as myofilaments. Such myofilaments have been found in skeletal muscle. Other studies have indicated that individual myofibrillar proteins can exchange with their counterparts in the cytoplasm; it is unclear whether this can be done to an extent that is consistent with the rate of myofibrillar protein turnover in living muscle. It seems that both the calpains and the proteasome are responsible for myofibrillar protein turnover, but the mechanism is still unknown.