Abstract
BackgroundTetraspanins 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.MethodsWe 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.ResultsExpression 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.ConclusionBasal 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.
Highlights
Tetraspanins are a family of proteins known to assemble protein complexes at the cell membrane
Our previous study identified CD82 as an effective marker to prospectively isolate human muscle stem cells and found its expression variably decreased in cell lines and muscle tissues from patients with Duchenne muscular dystrophy [14]
The genotype of CD82−/− mice was first confirmed by PCR and RT/PCR (Supplementary Figure 1A) followed by sequence analysis on RNA extracted from WT and CD82−/− skeletal muscle
Summary
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, bringing complexity and diversity in their regulatory networks. The tetraspanins are a class of transmembrane proteins known to regulate the assembly of protein complexes at the cell membrane [1,2,3,4]. While CD82 expression is fairly ubiquitous, there is variation in the transcripts encoded with some isoforms lacking the C-terminus or transcript variants lacking specific exons [17] While these transcriptional variants are known, their specific function has not been elucidated
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