Tropomodulin Capping of Actin Filaments in Striated Muscle Development and Physiology

Figure 3

Model diagram of Tmods in the sarcomeres and SR of skeletal muscle. Thin filaments, consisting of α-actin subunits, are capped at their pointed ends by a combination of Tmod1 and Tmod4 in skeletal muscle, whereas Tmod3 is associated with cytoplasmic (nonmuscle) γ-actin filaments in the SR. The exact stoichiometries and distributions of Tmod1 versus Tmod4 on the thin filament pointed ends are unknown. Tmod-capped thin filaments extend past the distal N-terminus of nebulin into the middle of the sarcomere. By contrast, in cardiac muscle (not shown here), thin filament pointed ends are capped solely by Tmod1 and do not contain nebulin. Filaments composed of γ-actin, nonmuscle TMs, and Tmod3 are anchored to the SR membrane via sAnk1.5 and laterally connected by a spectrin network. Tmod3/nonmuscle TM/γ-actin filaments are connected to myofibrils via Tmod3 binding to sAnk1.5, which links to obscurin, which, in turn, is linked to myomesin and titin at the M-line. To date, Tmod3’s localization with respect to the cardiac SR remains undetermined. Note that for clarity, the thick filaments are not drawn to scale with respect to the thin filaments.