The sarcoplasmic reticulum: Actin and tropomodulin hit the links.

Skeletal muscle exhibits strikingly regular intracellular sorting of actin and tropomodulin (Tmod) isoforms, which are essential for efficient muscle contraction. A recent study from our laboratory demonstrates that the skeletal muscle sarcoplasmic reticulum (SR) is associated with cytoplasmic γ-actin (γ(cyto)-actin) filaments, which are predominantly capped by Tmod3. When Tmod3 is experimentally induced to vacate its SR compartment, the cytoskeletal organization of SR-associated γ(cyto)-actin is perturbed, leading to SR swelling, depressed SR Ca(2+) release and myofibril misalignment. Based on these findings, Tmod3-capped γ(cyto)-actin filaments mechanically stabilize SR structure and regulate SR function via a novel lateral linkage. Furthermore, by placing these findings in the context of studies in nonmuscle cells, we conclude that Tmodcapped actin filaments are emerging as critical regulators of membrane stability and physiology in a broad assortment of cell types.