title: Sarcospan reduces dystrophic pathology: stabilization of the utrophin-glycoprotein complex.
abstract: Mutations in the dystrophin gene cause Duchenne muscular dystrophy and result in the loss of dystrophin and the entire dystrophin-glycoprotein complex (DGC) from the sarcolemma. We show that sarcospan (SSPN), a unique tetraspanin-like component of the DGC, ameliorates muscular dystrophy in dystrophin-deficient mdx mice. SSPN stabilizes the sarcolemma by increasing levels of the utrophin-glycoprotein complex (UGC) at the extrasynaptic membrane to compensate for the loss of dystrophin. Utrophin is normally restricted to the neuromuscular junction, where it replaces dystrophin to form a functionally analogous complex. SSPN directly interacts with the UGC and functions to stabilize utrophin protein without increasing utrophin transcription. These findings reveal the importance of protein stability in the prevention of muscular dystrophy and may impact the future design of therapeutics for muscular dystrophies.
authors.affiliation: Department of Physiological Science and 2Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Angela K
authors.initials: AK
authors.lastname: Peter
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Marshall
authors.forename: Rachelle H
authors.initials: RH
authors.lastname: Crosbie
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D016189:Dystrophin / Q000172:deficiency / Q000235:genetics; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D018101:Mice, Inbred mdx; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology / Q000517:prevention & control*; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D012508:Sarcolemma / Q000502:physiology; D014158:Transcription, Genetic; D049411:Utrophin / Q000235:genetics / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D016189:Dystrophin; D006023:Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C109646:SSPN protein, human; D049411:Utrophin