Sarcospan

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
Identifiers
SymbolSSPN
NCBI gene8082
HGNC11322
OMIM601599
Other data
LocusChr. 12 p11.2

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. Marshall JL, Crosbie-Watson RH (January 2013). "Sarcospan: a small protein with large potential for Duchenne muscular dystrophy" (PDF). Skeletal Muscle. 3 (1): 1. doi:10.1186/2044-5040-3-1. PMC 3599653. PMID 23282144.
  2. Crosbie RH, Heighway J, Venzke DP, Lee JC, Campbell KP (December 1997). "Sarcospan, the 25-kDa transmembrane component of the dystrophin-glycoprotein complex". The Journal of Biological Chemistry. 272 (50): 31221–4. doi:10.1074/jbc.272.50.31221. PMID 9395445.
  3. Peter AK, Marshall JL, Crosbie RH (November 2008). "Sarcospan reduces dystrophic pathology: stabilization of the utrophin-glycoprotein complex". The Journal of Cell Biology. 183 (3): 419–27. doi:10.1083/jcb.200808027. PMC 2575773. PMID 18981229.
  4. Marshall JL, Oh J, Chou E, Lee JA, Holmberg J, Burkin DJ, Crosbie-Watson RH (April 2015). "Sarcospan integration into laminin-binding adhesion complexes that ameliorate muscular dystrophy requires utrophin and α7 integrin". Human Molecular Genetics. 24 (7): 2011–22. doi:10.1093/hmg/ddu615. PMC 4355028. PMID 25504048.
  5. Marshall JL, Holmberg J, Chou E, Ocampo AC, Oh J, Lee J, Peter AK, Martin PT, Crosbie-Watson RH (June 2012). "Sarcospan-dependent Akt activation is required for utrophin expression and muscle regeneration". The Journal of Cell Biology. 197 (7): 1009–27. doi:10.1083/jcb.201110032. PMC 3384411. PMID 22734004.
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