Integration of troponin I phosphorylation with cardiac regulatory networks.

We focus here on the modulation of thin filament activity by cardiac troponin I phosphorylation as an integral and adaptive mechanism in cardiac homeostasis and as a mechanism vulnerable to maladaptive response to stress. We discuss a current concept of cardiac troponin I function in the A-band region of the sarcomere and potential signaling to cardiac troponin I in a network involving the ends of the thin filaments at the Z-disk and the M-band regions. The cardiac sarcomere represents a remarkable set of interacting proteins that functions not only as a molecular machine generating the heartbeat but also as a hub of signaling. We review how phosphorylation signaling to cardiac troponin I is integrated, with parallel signals controlling excitation-contraction coupling, hypertrophy, and metabolism.