Mechanism of Catch Force: Tethering of Thick and Thin Filaments by Twitchin
Figure 13
A model showing twitchin interaction with thick and thin filaments during the myosin crossbridge cycle. (a) The relaxed state. The myosin crossbridge is in the low-force state and detached from the thin filament. The regulatory sites in twitchin are phosphorylated, and twitchin is detached from the thin filament. (b) The prepower stroke state. The myosin crossbridge has been activated by an increase in [Ca+2] and the crossbridge binds to the thin filament. Twitchin has been displaced from the thin filament as a result of crossbridge binding to the thin filament. Twitchin is also dephosphorylated by activation of the phosphatase calcineurin. (c) The high-force state. Myosin has gone through the power stroke resulting in force generation. Twitchin is detached from the thin filament by myosin interaction with the thin filament. (d) The catch state. Myosin is in the low-force state and detached from the thin filament. Unphosphorylated twitchin is attached to both the thick and thin filaments. Phosphorylation of twitchin would result in detachment of twitchin from the thin filament and lead to the relaxed state (a). The myosin-twitchin-thin filament interactions described apply independently to both the N- and C-terminal regions of twitchin as shown in the “belt and suspenders” cartoon in Figure 12.
