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: Angela K Peter, Jamie L Marshall, Rachelle H Crosbie
• Journal: The Journal of cell biology (J Cell Biol) Vol. 183 Issue 3 Pg. 419-27 (Nov 03 2008) ISSN: 1540-8140 [Electronic] United States
• PMID: 18981229 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Dystrophin
• Glycoproteins
• Membrane Proteins
• Neoplasm Proteins
• SSPN protein, human
• Utrophin

Topics

• Animals
• Carrier Proteins (genetics, physiology)
• Dystrophin (deficiency, genetics)
• Glycoproteins (physiology)
• Humans
• Membrane Proteins (genetics, physiology)
• Mice
• Mice, Inbred mdx
• Mice, Transgenic
• Muscle, Skeletal (pathology, physiology, physiopathology)
• Muscular Dystrophy, Duchenne (pathology, prevention & control)
• Neoplasm Proteins (genetics, physiology)
• Sarcolemma (physiology)
• Transcription, Genetic
• Utrophin (genetics, physiology)