Peter et al. now show that adding it to muscle cells might ameliorate the most severe form of muscular dystrophy.

In Duchenne muscular dystrophy (DMD), the mutated dystrophin protein fails to anchor correctly to its membrane glycoprotein complex. And without this anchoring, muscle cells experience severe contraction-induced damage. Sarcospan is part of the anchoring complex, but because mice without sarcospan don't seem any worse for its absence, it hasn't received much attention. Sarcospan's structure, however, suggests it might help stabilize the membrane complex, so the authors decided to test the effects of increasing sarcospan expression in a DMD mouse model.

The increase did not improve the dystrophin “glycoprotein interaction, but instead, the team was surprised to find sarcospan coaxed a dystrophin relative called utrophin to spread out on the muscle membrane. Utrophin is normally restricted to the neuromuscular junction, where it serves a role similar to that of dystrophin.

The extra sarcospan prompted higher levels of utrophin in the cell, but not by increasing its expression. Sarcospan instead stabilized extrajunctional utrophin complexes, which normally form early in development and then disappear after the first few weeks of life.

Mouse muscle cells were protected by sarcospan, but the true importance of this discovery will lie in its potential for human therapeutics, specifically gene therapy. In that regard, sarcospan's small gene size is significant - at 600 bp, it is easily packaged into the safest viral vectors, unlike either dystrophin or utrophin, which are about 700 times larger and require more immunogenic vectors.

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"That is a very high effect for a mental illness, because most mental illnesses have many potential causes," Provencio noted. "A mental illness may arise from many mutations, and we have found one that has a clear link."

The melanopsin gene encodes a light-sensitive protein that is found in a class of photoreceptors in the retina that are not involved with vision, but are linked to many non-visual responses, such as the control of circadian rhythms, the control of hormones, the mediation of alertness and the regulation of sleep.

The mutation in this gene may result in aberrant regulation of these responses to light, leading to the depressive symptoms of SAD. About 29 percent of SAD patients come from families with a history of the disorder, suggesting a genetic or hereditary link.

"The finding suggest that melanopsin mutations may predispose some people to SAD, and that if you have two copies of this mutation, there is a very high probability that you will be afflicted," Provencio said. "An eventual understanding of the mechanisms underlying the pathological response to light in SAD may lead to improved treatments."

Provencio adds that the finding, with further study, could also lead to improved testing for SAD.

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