Sensory adaptation in inner ear hair cells depends on myosin‑1c (Myo1c), the molecular motor that regulates mechanotransduction channel sensitivity. This dissertation examines how protein kinase A (PKA) phosphorylation modulates Myo1c function. We demonstrate that Myo1c can be phosphorylated by PKA at serine 701 (S701) under specific calcium and calmodulin-dependent conditions, though phosphorylation is inefficient in cells. Mutations at S701 significantly alter ATPase activity, actin translocation velocity, and force production, indicating a critical role for this site in motor mechanics. Additional in vitro studies suggest that Myo1c tail domains contribute to efficient motility and force generation. Together, these findings reveal complex regulatory mechanisms controlling Myo1c activity and support a role for PKA signaling in hair cell adaptation.
