Myofibre Hyper-Contractility in Horses Expressing the Myosin Heavy Chain Myopathy Mutation, MYH1(E321G).
Myofibre Hyper-Contractility in Horses Expressing the Myosin Heavy Chain Myopathy Mutation, MYH1(E321G).
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DOI：
10.3390/cells10123428
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发表时间：
2021-12-06
期刊：
影响因子：
6
通讯作者：
Valberg SJ
中科院分区：
文献类型：
--
作者：
Ochala J;Finno CJ;Valberg SJ
肌球蛋白病被定义为一组以编码肌球蛋白重链的基因突变为特征的肌肉疾病。其确切的分子和细胞机制尚不清楚。在本研究中，我们将注意力集中在MYH 1相关的E321 G氨基酸取代的IIx型骨骼肌肌球蛋白重链的头部区域内，与临床症状的萎缩，炎症和/或深刻的横纹肌溶解症，被称为马肌球蛋白重链肌病。我们对来自对照马（MYH 1 E321 G −/−）和E321 G突变纯合子（MYH 1 E321 G +/+）或杂合子（MYH 1 E321 G +/−）的夸特马的分离IIx肌纤维进行了Mant-ATP追踪实验和力测量。单残基置换不影响肌球蛋白分子的松弛构象。然而，与MYH 1 E321 G +/−和MYH 1 E321 G −/−马相比，MYH 1 E321 G +/+马的最大力产生和Ca 2+敏感性更高，证明其显著增加了其主动行为。总之，这些研究结果表明，在E321 G突变的存在下，分子和细胞的超收缩表型发生，这可能有助于肌球蛋白重链肌病的发展。
Myosinopathies are defined as a group of muscle disorders characterized by mutations in genes encoding myosin heavy chains. Their exact molecular and cellular mechanisms remain unclear. In the present study, we have focused our attention on a MYH1-related E321G amino acid substitution within the head region of the type IIx skeletal myosin heavy chain, associated with clinical signs of atrophy, inflammation and/or profound rhabdomyolysis, known as equine myosin heavy chain myopathy. We performed Mant-ATP chase experiments together with force measurements on isolated IIx myofibres from control horses (MYH1E321G−/−) and Quarter Horses homozygous (MYH1E321G+/+) or heterozygous (MYH1E321G+/−) for the E321G mutation. The single residue replacement did not affect the relaxed conformations of myosin molecules. Nevertheless, it significantly increased its active behaviour as proven by the higher maximal force production and Ca2+ sensitivity for MYH1E321G+/+ in comparison with MYH1E321G+/− and MYH1E321G−/− horses. Altogether, these findings indicate that, in the presence of the E321G mutation, a molecular and cellular hyper-contractile phenotype occurs which could contribute to the development of the myosin heavy chain myopathy.
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影响因子：
2.6
作者：
Durward-Akhurst SA;Finno CJ;Barnes N;Shivers J;Guo LT;Shelton GD;Valberg SJ
通讯作者：
Valberg SJ
影响因子：
11.2
作者：
Lindqvist J;Levy Y;Pati-Alam A;Hardeman EC;Gregorevic P;Ochala J
通讯作者：
Ochala J
影响因子：
37.8
作者：
Toepfer, Christopher N.;Garfinkel, Amanda C.;Seidman, Christine E.
通讯作者：
Seidman, Christine E.
DOI：
10.1097/nen.0b013e318293b1cc
发表时间：
2013-06-01
影响因子：
3.2
作者：
Lindqvist, Johan;Cheng, Arthur J.;Ochala, Julien
通讯作者：
Ochala, Julien
影响因子：
3.7
作者：
Ochala, Julien;Ravenscroft, Gianina;Nowak, Kristen J.
通讯作者：
Nowak, Kristen J.