Molecular mimicking of C-terminal phosphorylation tunes the surface dynamics of CaV1.2 calcium channels in hippocampal neurons

摘要: L-type voltage-gated CaV1.2 calcium channels (CaV1.2) are key regulators of neuronal excitability, synaptic plasticity, and excitation-transcription coupling. Surface-exposed distributes in clusters along the dendrites hippocampal neurons. A permanent exchange between stably clustered laterally diffusive extra-clustered maintains steady-state levels at dendritic signaling domains. dynamic equilibrium anchored receptors is a common feature among ion crucial to modulate transduction. Despite importance this fine regulatory system, molecular mechanisms underlying surface dynamics completely unexplored. Here, we examined states depending on phosphorylation Ser-1700 Ser-1928 channel C terminus. Phosphorylation these sites strongly involved CaV1.2-mediated nuclear factor activated T cells (NFAT) signaling, long-term potentiation, responsiveness adrenergic stimulation. We engineered constructs mimicking analyzed their behavior membrane by immunolabeling protocols, fluorescence recovery after photobleaching, single particle tracking. found that phosphomimetic S1928E variant increases mobility without altering maintenance cluster young neurons favors stabilization later differentiation. Instead, promoted state irrespective differentiation stage. Together, results reveal could contribute establishment anchoring state. Finally, our findings suggest novel mechanism which terminus regulates tuning content complexes.