Nebulin, a multi-functional giant

Efficient muscle contraction in skeletal muscle is predicated on the regulation ofactin filament lengths.Inone long-standing model that was prominent for decades, the giant protein nebulin was proposed to functionas a 'molecular ruler' tospecify the lengths ofthe thin filaments. This theory was questioned by many observations, including experiments in which the length of nebulin was manipulated in skeletal myocytes; this approach revealed that nebulin functions to stabilize filamentous actin, allowing thin filaments to reach mature lengths. In addition, more recent data, mostly from in vivo models and identification of new interacting partners, have provided evidence that nebulin is not merely a structural protein. Nebulin plays a role in numerous cellular processes including regulation of muscle contraction, Z-disc formation, and myofibril organization and assembly.