Tetraspanin CD82 is necessary for muscle stem cell activation and supports dystrophic muscle function. Skelet Muscle 2020 Nov 27;10(1):34
Date
11/28/2020Pubmed ID
33243288Pubmed Central ID
PMC7693590DOI
10.1186/s13395-020-00252-3Scopus ID
2-s2.0-85096675863 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
BACKGROUND: Tetraspanins are a family of proteins known to assemble protein complexes at the cell membrane. They are thought to play diverse cellular functions in tissues by modifying protein-binding partners, thus bringing complexity and diversity in their regulatory networks. Previously, we identified the tetraspanin KAI/CD82 as a prospective marker for human muscle stem cells. CD82 expression appeared decreased in human Duchenne muscular dystrophy (DMD) muscle, suggesting a functional link to muscular dystrophy, yet whether this decrease is a consequence of dystrophic pathology or a compensatory mechanism in an attempt to rescue muscle from degeneration is currently unknown.
METHODS: We studied the consequences of loss of CD82 expression in normal and dystrophic skeletal muscle and examined the dysregulation of downstream functions in mice aged up to 1 year.
RESULTS: Expression of CD82 is important to sustain satellite cell activation, as in its absence there is decreased cell proliferation and less efficient repair of injured muscle. Loss of CD82 in dystrophic muscle leads to a worsened phenotype compared to control dystrophic mice, with decreased pulmonary function, myofiber size, and muscle strength. Mechanistically, decreased myofiber size in CD82-/- dystrophic mice is not due to altered PTEN/AKT signaling, although increased phosphorylation of mTOR at Ser2448 was observed.
CONCLUSION: Basal CD82 expression is important to dystrophic muscle, as its loss leads to significantly weakened myofibers and impaired muscle function, accompanied by decreased satellite cell activity that is unable to protect and repair myofiber damage.
Author List
Hall A, Fontelonga T, Wright A, Bugda Gwilt K, Widrick J, Pasut A, Villa F, Miranti CK, Gibbs D, Jiang E, Meng H, Lawlor MW, Gussoni EAuthor
Michael W. Lawlor MD, PhD Adjunct Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Proliferation
Cells, Cultured
Female
Kangai-1 Protein
Male
Mice
Mice, Inbred C57BL
Muscle Strength
Muscular Dystrophy, Duchenne
PTEN Phosphohydrolase
Proto-Oncogene Proteins c-akt
Satellite Cells, Skeletal Muscle
Signal Transduction
TOR Serine-Threonine Kinases
