Tetraspanin CD82 is necessary for muscle stem cell activation and supports dystrophic muscle function.
Animals
Cell Proliferation
Cells, Cultured
Female
Kangai-1 Protein
/ genetics
Male
Mice
Mice, Inbred C57BL
Muscle Strength
Muscular Dystrophy, Duchenne
/ genetics
PTEN Phosphohydrolase
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Satellite Cells, Skeletal Muscle
/ metabolism
Signal Transduction
TOR Serine-Threonine Kinases
/ metabolism
AKT
Muscular dystrophy
Regeneration
Stem cells
Tetraspanin
mTOR
Journal
Skeletal muscle
ISSN: 2044-5040
Titre abrégé: Skelet Muscle
Pays: England
ID NLM: 101561193
Informations de publication
Date de publication:
27 11 2020
27 11 2020
Historique:
received:
01
06
2020
accepted:
09
11
2020
entrez:
27
11
2020
pubmed:
28
11
2020
medline:
5
10
2021
Statut:
epublish
Résumé
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. 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. 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 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.
Sections du résumé
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
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.
Identifiants
pubmed: 33243288
doi: 10.1186/s13395-020-00252-3
pii: 10.1186/s13395-020-00252-3
pmc: PMC7693590
doi:
Substances chimiques
Cd82 antigen, mouse
0
Kangai-1 Protein
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
PTEN Phosphohydrolase
EC 3.1.3.67
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
34Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR069582
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD090255
Pays : United States
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