Figure 6: A molecular ruler governs ROCK access to substrates.
From: A molecular ruler regulates cytoskeletal remodelling by the Rho kinases
ROCK-mediated actomyosin contraction. Functional model of ROCK with respect to the plasma membrane, focal adhesions and components of the actomyosin contractile machinery, including ROCK substrates, found in the actin cortex. All components are drawn approximately to scale. ROCK binds to the plasma membrane via its ‘split’ PH and C1 domains, although the precise nature of the membrane ligands is as yet unknown. The coiled-coil of ROCK bridges the membrane to substrates located in the actin cortex at a distance of 120 nm. Scaffold proteins, such as Shroom, may serve to stabilize the orientation and/or flexibility of the coiled-coil, thereby restricting the conformational space sampled by the catalytic domains. Short conserved segments of the coiled-coil (indicated with closed circles) may serve as interaction surfaces for scaffold proteins. The link between RhoA, ROCK and downstream actomyosin contraction remains to be determined. We hypothesize that force transducers, such as talin and vinculin, regulate the positioning of the cytoskeletal machinery, and thus ROCK substrates such as MLC2 and MYPT1, with respect to focal adhesions and the plasma membrane.
