Sarcospan
| sarcospan | |
|---|---|
| Identifiers | |
| Symbol | SSPN |
| Entrez | 8082 |
| HUGO | 11322 |
| OMIM | 601599 |
| Other data | |
| Locus | Chr. 12 p11.2 |
Originally identified as Kirsten ras associated gene (krag),[1] Sarcospan (SSPN) (is a 25-kDa transmembrane protein located in the dystrophin-associated protein complex of skeletal muscle cells, where it is most abundant.[1] It contains four transmembrane spanning helices with both N- and C-terminal domains located intracellularly.[2] Loss of SSPN expression occurs in patients with Duchenne muscular dystrophy. Dystrophin is required for proper localization of SSPN.[2] SSPN is also an essential regulator of Akt signaling pathways. Without SSPN, Akt signaling pathways will be hindered and muscle regeneration will not occur.[1]
Sarcospan in Muscular Dystrophy
The loss of dystrophin results in muscular dystrophy.[3] SSPN upregulates the levels of Utrophin-glycoprotein complex (UGC) to make up for the loss of dystrophin in the neuromuscular junction.[3] Sarcoglycans bind to SSPN and form the SG-SSPN complex, which interacts with dystroglycans (DG) and Utrophin leading to the formation of the UGC.[4] SSPN regulates the amount of Utrophin produced by the UGC to restore laminin binding due to the absence of dystrophin.[5] If laminin binding is not restored by SSPN, contraction of the membrane is present.[5] In dystrophic mdx mice, SSPN increases levels of Utrophin and restores the levels of laminin binding, reducing the symptoms of muscular dystrophy [5]
References
- 1 2 3 Marshall, Jamie L; Crosbie-Watson, Rachelle H (2013). "Sarcospan: a small protein with large potential for Duchenne muscular dystrophy". Skeletal Muscle. 3 (1): 1. doi:10.1186/2044-5040-3-1.
- 1 2 Crosbie; Heighway, J; Venzke, DP; Lee, JC; Campbell, KP; et al. (1997). "Sarcospan, the 25-kDa transmembrane component of the dystrophin-glycoprotein complex". J Biol Chem. 272 (50): 31221–4. doi:10.1074/jbc.272.50.31221. PMID 9395445.
- 1 2 Peter, Angela K.; Marshall, Jamie L.; Crosbie, Rachelle H. (3 November 2008). "Sarcospan reduces dystrophic pathology: stabilization of the utrophin–glycoprotein complex". The Journal of Cell Biology. 183 (3): 419–427. doi:10.1083/jcb.200808027.
- ↑ Marshall, J. L.; Oh, J.; Chou, E.; Lee, J. A.; Holmberg, J.; Burkin, D. J.; Crosbie-Watson, R. H. (11 December 2014). "Sarcospan integration into laminin-binding adhesion complexes that ameliorate muscular dystrophy requires utrophin and 7 integrin". Human Molecular Genetics. 24 (7): 2011–2022. doi:10.1093/hmg/ddu615.
- 1 2 3 Marshall, Jamie L.; Holmberg, Johan; Chou, Eric; Ocampo, Amber C.; Oh, Jennifer; Lee, Joy; Peter, Angela K.; Martin, Paul T.; Crosbie-Watson, Rachelle H. (25 June 2012). "Sarcospan-dependent Akt activation is required for utrophin expression and muscle regeneration". The Journal of Cell Biology. 197 (7): 1009–1027. doi:10.1083/jcb.201110032.
External links
- Sarcospan at the US National Library of Medicine Medical Subject Headings (MeSH)