Fernandes and Schöck reveal that Drosophila make do with a much shorter version of the actin-binding muscle protein nebulin.
Nebulin is a giant protein that contains 185 actin-binding repeats and aligns with muscle thin filaments by extending from the Z-discs at the ends of sarcomeres. Mutations in nebulin reduce thin filament length and cause the muscle disease nemaline myopathy. Lasp, the only nebulin-related protein in Drosophila, is a much smaller protein that contains just two nebulin repeats. Lasp controls the actin cytoskeleton in germline cells, but its function in fly muscles is unknown.
Fernandes and Schöck found that flies lacking Lasp showed several defects in sarcomeric structure: their thin filaments were shorter, their thin and thick filaments were spaced further apart, and the I-band region around the Z-discs was disorganized. Compensating for its smaller size, Lasp controlled these different aspects of muscle structure by localizing to two distinct regions of the sarcomere. The protein bound to α-actinin in the Z-discs, stabilizing I-band architecture by anchoring a member of the titin family of elastic muscle proteins, and also localized to the A-band, where thin and thick filaments overlap.
Lasp therefore makes do with just two nebulin repeats, and Fernandes and Schöck found that each repeat has a different function. The first is involved in binding to α-actinin, whereas the second binds to myosin, recruiting Lasp to the A-band to regulate filament spacing. Author Frieder Schöck now wants to analyze this latter interaction in more detail.
Text by Ben Short