831. The work suggests that reduced levels of SMA's signature protein, SMN, disrupt the junction from the muscle side.
SMA is the second most prevalent fatal recessive illness after cystic fibrosis. Although its severity varies, the disease often kills patients before age two as motoneurons deteriorate and muscles wither. How reduced amounts of SMN trigger symptoms isn't clear. Because the disease involves neural breakdown, researchers have assumed that the loss of SMN mainly hits motoneurons, not muscles.
To model the disease, Rajendra et al. identified fruit flies that produce too little of the protein. Feeble flight muscles grounded the mutants. Consistent with previous mouse models, the neurons that innervate these weakened muscles grew and branched abnormally. In addition, the insects' flight muscles lacked actin, a sign that innervation had failed.
Localization experiments suggested SMN is crucial specifically in muscles. The researchers determined that, in normal flies, SMN accumulates in muscle sarcomeres and gloms onto α-actinin, which interlinks actin filaments. Although the results do not rule out the “neuron first” hypothesis, they suggest that muscle dysfunction helps spur nerve deterioration.