Post-Translational Modification of Cav1.2 and its Role in Neurodegenerative Diseases

FIGURE 1. Cav1.2 state transitions during activation [modified after (Beyl et al., 2009) (Hering et al., 2018)]. The channel gating is determined by two functionally distinct processes: a voltage-sensing mechanism and a conducting pore. These two processes defined 4 states: R, at rest, pore is closed and S4 segments in the “down” position lock the pore. A, when depolarized, voltage-sensing mechanism is activated and S4 segments move to the “up” position and release the pore; but the pore remains closed. O, during continuous depolarization, all four S4 segments are in the “up” position; the pore is open. D, when returned to the resting potential, the deactivated voltage-sensing segment moved toward a “down” position while the pore is still open. Subsequently, the pore will transit to its closed conformation and at a resting state.

FIGURE 2. Schematic representation of the PTM of Cav1.2 and its correlation with neurodegenerative diseases. The PTM changes the channel activity, degradation, and cell surface expression of Cav1.2. The PTM of Cav1.2 or the disruption of their regulating pathways was also observed in neurodegenerative diseases.