Originally identified as Kirsten ras associated gene (krag),
Sarcospan (SSPN) is a 25-kDa
transmembrane protein
A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequent ...
located in the
dystrophin-associated protein complex The dystrophin-associated protein complex, also known as the dystrophin-associated glycoprotein complex is a multiprotein complex that includes dystrophin and the dystrophin-associated proteins. It is one of the two protein complexes that make up ...
of
skeletal muscle
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of m ...
cells, where it is most abundant.
It contains four transmembrane spanning helices with both N- and C-terminal domains located intracellularly.
Loss of SSPN expression occurs in patients with
Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy that primarily affects boys. Muscle weakness usually begins around the age of four, and worsens quickly. Muscle loss typically occurs first in the thighs and pelvis follow ...
.
Dystrophin
Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the cost ...
is required for proper localization of SSPN.
SSPN is also an essential regulator of Akt signaling pathways. Without SSPN, Akt signaling pathways will be hindered and muscle regeneration will not occur.
Sarcospan in Muscular Dystrophy
The loss of dystrophin results in muscular dystrophy.
SSPN upregulates the levels of Utrophin-glycoprotein complex (UGC) to make up for the loss of dystrophin in the neuromuscular junction.
Sarcoglycans bind to SSPN and form the SG-SSPN complex, which interacts with dystroglycans (DG) and Utrophin leading to the formation of the UGC.
SSPN regulates the amount of Utrophin produced by the UGC to restore laminin binding due to the absence of dystrophin.
If laminin binding is not restored by SSPN, contraction of the membrane is present.
In dystrophic mdx mice, SSPN increases levels of Utrophin and restores the levels of laminin binding, reducing the symptoms of muscular dystrophy
References
External links
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