In Skeletal Muscle Fibers, Protein Kinase Subunit CSNK2A1/CK2α Is Required for Proper Muscle Homeostasis and Structure and Function of Neuromuscular Junctions
CSNK2 tetrameric holoenzyme is composed of two subunits with catalytic activity (CSNK2A1 and/or CSNK2A2) and two regulatory subunits (CSNK2B) and is involved in skeletal muscle homeostasis. Up-to-date, constitutive Csnk2a2 knockout mice demonstrated mild regenerative impairments in skeletal muscles,...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/24/3962 |
| _version_ | 1797460930173337600 |
|---|---|
| author | Mira Merholz Yongzhi Jian Johannes Wimberg Lea Gessler Said Hashemolhosseini |
| author_facet | Mira Merholz Yongzhi Jian Johannes Wimberg Lea Gessler Said Hashemolhosseini |
| author_sort | Mira Merholz |
| collection | DOAJ |
| description | CSNK2 tetrameric holoenzyme is composed of two subunits with catalytic activity (CSNK2A1 and/or CSNK2A2) and two regulatory subunits (CSNK2B) and is involved in skeletal muscle homeostasis. Up-to-date, constitutive Csnk2a2 knockout mice demonstrated mild regenerative impairments in skeletal muscles, while conditional Csnk2b mice were linked to muscle weakness, impaired neuromuscular transmission, and metabolic and autophagic compromises. Here, for the first time, skeletal muscle-specific conditional Csnk2a1 mice were generated and characterized. The ablation of Csnk2a1 expression was ensured using a human skeletal actin-driven Cre reporter. In comparison with control mice, first, conditional knockout of CSNK2A1 resulted in age-dependent reduced grip strength. Muscle weakness was accompanied by impaired neuromuscular transmission. Second, the protein amount of other CSNK2 subunits was aberrantly changed. Third, the number of central nuclei in muscle fibers indicative of regeneration increased. Fourth, oxidative metabolism was impaired, reflected by an increase in cytochrome oxidase and accumulation of mitochondrial enzyme activity underneath the sarcolemma. Fifth, autophagic processes were stimulated. Sixth, NMJs were fragmented and accompanied by increased synaptic gene expression levels. Altogether, knockout of Csnk2a1 or Csnk2b results in diverse impairments of skeletal muscle biology. |
| first_indexed | 2024-03-09T17:13:10Z |
| format | Article |
| id | doaj.art-32ee1ae1357c4cfabed3816b9689d9bf |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T17:13:10Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-32ee1ae1357c4cfabed3816b9689d9bf2023-11-24T13:53:28ZengMDPI AGCells2073-44092022-12-011124396210.3390/cells11243962In Skeletal Muscle Fibers, Protein Kinase Subunit CSNK2A1/CK2α Is Required for Proper Muscle Homeostasis and Structure and Function of Neuromuscular JunctionsMira Merholz0Yongzhi Jian1Johannes Wimberg2Lea Gessler3Said Hashemolhosseini4Institute of Biochemistry, Medical Faculty, Friedrich-Alexander-University of Erlangen-Nürnberg, 91054 Erlangen, GermanyInstitute of Biochemistry, Medical Faculty, Friedrich-Alexander-University of Erlangen-Nürnberg, 91054 Erlangen, GermanyInstitute of Biochemistry, Medical Faculty, Friedrich-Alexander-University of Erlangen-Nürnberg, 91054 Erlangen, GermanyInstitute of Biochemistry, Medical Faculty, Friedrich-Alexander-University of Erlangen-Nürnberg, 91054 Erlangen, GermanyInstitute of Biochemistry, Medical Faculty, Friedrich-Alexander-University of Erlangen-Nürnberg, 91054 Erlangen, GermanyCSNK2 tetrameric holoenzyme is composed of two subunits with catalytic activity (CSNK2A1 and/or CSNK2A2) and two regulatory subunits (CSNK2B) and is involved in skeletal muscle homeostasis. Up-to-date, constitutive Csnk2a2 knockout mice demonstrated mild regenerative impairments in skeletal muscles, while conditional Csnk2b mice were linked to muscle weakness, impaired neuromuscular transmission, and metabolic and autophagic compromises. Here, for the first time, skeletal muscle-specific conditional Csnk2a1 mice were generated and characterized. The ablation of Csnk2a1 expression was ensured using a human skeletal actin-driven Cre reporter. In comparison with control mice, first, conditional knockout of CSNK2A1 resulted in age-dependent reduced grip strength. Muscle weakness was accompanied by impaired neuromuscular transmission. Second, the protein amount of other CSNK2 subunits was aberrantly changed. Third, the number of central nuclei in muscle fibers indicative of regeneration increased. Fourth, oxidative metabolism was impaired, reflected by an increase in cytochrome oxidase and accumulation of mitochondrial enzyme activity underneath the sarcolemma. Fifth, autophagic processes were stimulated. Sixth, NMJs were fragmented and accompanied by increased synaptic gene expression levels. Altogether, knockout of Csnk2a1 or Csnk2b results in diverse impairments of skeletal muscle biology.https://www.mdpi.com/2073-4409/11/24/3962CSNK2A1CSNK2A2CSNK2Bprotein kinase CK2skeletal musclemyogenesis |
| spellingShingle | Mira Merholz Yongzhi Jian Johannes Wimberg Lea Gessler Said Hashemolhosseini In Skeletal Muscle Fibers, Protein Kinase Subunit CSNK2A1/CK2α Is Required for Proper Muscle Homeostasis and Structure and Function of Neuromuscular Junctions Cells CSNK2A1 CSNK2A2 CSNK2B protein kinase CK2 skeletal muscle myogenesis |
| title | In Skeletal Muscle Fibers, Protein Kinase Subunit CSNK2A1/CK2α Is Required for Proper Muscle Homeostasis and Structure and Function of Neuromuscular Junctions |
| title_full | In Skeletal Muscle Fibers, Protein Kinase Subunit CSNK2A1/CK2α Is Required for Proper Muscle Homeostasis and Structure and Function of Neuromuscular Junctions |
| title_fullStr | In Skeletal Muscle Fibers, Protein Kinase Subunit CSNK2A1/CK2α Is Required for Proper Muscle Homeostasis and Structure and Function of Neuromuscular Junctions |
| title_full_unstemmed | In Skeletal Muscle Fibers, Protein Kinase Subunit CSNK2A1/CK2α Is Required for Proper Muscle Homeostasis and Structure and Function of Neuromuscular Junctions |
| title_short | In Skeletal Muscle Fibers, Protein Kinase Subunit CSNK2A1/CK2α Is Required for Proper Muscle Homeostasis and Structure and Function of Neuromuscular Junctions |
| title_sort | in skeletal muscle fibers protein kinase subunit csnk2a1 ck2α is required for proper muscle homeostasis and structure and function of neuromuscular junctions |
| topic | CSNK2A1 CSNK2A2 CSNK2B protein kinase CK2 skeletal muscle myogenesis |
| url | https://www.mdpi.com/2073-4409/11/24/3962 |
| work_keys_str_mv | AT miramerholz inskeletalmusclefibersproteinkinasesubunitcsnk2a1ck2aisrequiredforpropermusclehomeostasisandstructureandfunctionofneuromuscularjunctions AT yongzhijian inskeletalmusclefibersproteinkinasesubunitcsnk2a1ck2aisrequiredforpropermusclehomeostasisandstructureandfunctionofneuromuscularjunctions AT johanneswimberg inskeletalmusclefibersproteinkinasesubunitcsnk2a1ck2aisrequiredforpropermusclehomeostasisandstructureandfunctionofneuromuscularjunctions AT leagessler inskeletalmusclefibersproteinkinasesubunitcsnk2a1ck2aisrequiredforpropermusclehomeostasisandstructureandfunctionofneuromuscularjunctions AT saidhashemolhosseini inskeletalmusclefibersproteinkinasesubunitcsnk2a1ck2aisrequiredforpropermusclehomeostasisandstructureandfunctionofneuromuscularjunctions |