Myofibre Hyper-Contractility in Horses Expressing the Myosin Heavy Chain Myopathy Mutation, <i>MYH1<sup>E321G</sup></i>
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 <i>MYH1</i>-related E321G amino acid substitu...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/10/12/3428 |
| _version_ | 1797505988911169536 |
|---|---|
| author | Julien Ochala Carrie J. Finno Stephanie J. Valberg |
| author_facet | Julien Ochala Carrie J. Finno Stephanie J. Valberg |
| author_sort | Julien Ochala |
| collection | DOAJ |
| description | 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 <i>MYH1</i>-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 (<i>MYH1<sup>E321G−/−</sup></i>) and Quarter Horses homozygous (<i>MYH1<sup>E321G+/+</sup></i>) or heterozygous (<i>MYH1<sup>E321G+/−</sup></i>) 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 Ca<sup>2+</sup> sensitivity for <i>MYH1<sup>E321G+/+</sup></i> in comparison with <i>MYH1<sup>E321G+/−</sup></i> and <i>MYH1<sup>E321G−/−</sup></i> 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. |
| first_indexed | 2024-03-10T04:26:12Z |
| format | Article |
| id | doaj.art-d04bc37b376644afa6e4ce73e74291d9 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T04:26:12Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-d04bc37b376644afa6e4ce73e74291d92023-11-23T07:37:39ZengMDPI AGCells2073-44092021-12-011012342810.3390/cells10123428Myofibre Hyper-Contractility in Horses Expressing the Myosin Heavy Chain Myopathy Mutation, <i>MYH1<sup>E321G</sup></i>Julien Ochala0Carrie J. Finno1Stephanie J. Valberg2Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, DenmarkDepartment of Population Health and Reproduction, School of Veterinary Medicine, University of California at Davis, Davis, CA 95616, USALarge Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USAMyosinopathies 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 <i>MYH1</i>-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 (<i>MYH1<sup>E321G−/−</sup></i>) and Quarter Horses homozygous (<i>MYH1<sup>E321G+/+</sup></i>) or heterozygous (<i>MYH1<sup>E321G+/−</sup></i>) 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 Ca<sup>2+</sup> sensitivity for <i>MYH1<sup>E321G+/+</sup></i> in comparison with <i>MYH1<sup>E321G+/−</sup></i> and <i>MYH1<sup>E321G−/−</sup></i> 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.https://www.mdpi.com/2073-4409/10/12/3428congenital myopathyinflammationmyosin<i>MYH1</i>muscle fibremechanics |
| spellingShingle | Julien Ochala Carrie J. Finno Stephanie J. Valberg Myofibre Hyper-Contractility in Horses Expressing the Myosin Heavy Chain Myopathy Mutation, <i>MYH1<sup>E321G</sup></i> Cells congenital myopathy inflammation myosin <i>MYH1</i> muscle fibre mechanics |
| title | Myofibre Hyper-Contractility in Horses Expressing the Myosin Heavy Chain Myopathy Mutation, <i>MYH1<sup>E321G</sup></i> |
| title_full | Myofibre Hyper-Contractility in Horses Expressing the Myosin Heavy Chain Myopathy Mutation, <i>MYH1<sup>E321G</sup></i> |
| title_fullStr | Myofibre Hyper-Contractility in Horses Expressing the Myosin Heavy Chain Myopathy Mutation, <i>MYH1<sup>E321G</sup></i> |
| title_full_unstemmed | Myofibre Hyper-Contractility in Horses Expressing the Myosin Heavy Chain Myopathy Mutation, <i>MYH1<sup>E321G</sup></i> |
| title_short | Myofibre Hyper-Contractility in Horses Expressing the Myosin Heavy Chain Myopathy Mutation, <i>MYH1<sup>E321G</sup></i> |
| title_sort | myofibre hyper contractility in horses expressing the myosin heavy chain myopathy mutation i myh1 sup e321g sup i |
| topic | congenital myopathy inflammation myosin <i>MYH1</i> muscle fibre mechanics |
| url | https://www.mdpi.com/2073-4409/10/12/3428 |
| work_keys_str_mv | AT julienochala myofibrehypercontractilityinhorsesexpressingthemyosinheavychainmyopathymutationimyh1supe321gsupi AT carriejfinno myofibrehypercontractilityinhorsesexpressingthemyosinheavychainmyopathymutationimyh1supe321gsupi AT stephaniejvalberg myofibrehypercontractilityinhorsesexpressingthemyosinheavychainmyopathymutationimyh1supe321gsupi |