Endothelin and Phenylephrine Both Trigger Nuclear IP3 Elevation, but Differ in Ability to Activate Nuclear HDAC5 Export

Abstract

Within the channel, cargos move in a non-directional manner, consistent with anomalous subdiffusion in a crowded volume, with dimensions of ~55 nm in width and ~68 nm in length. By varying the number of import receptors on the surface of the cargo, we find that the translocation is not governed by simple receptor-NPC binding interactions and that the central channel behaves in accordance with the 'selective phase' model. Finally, in the absence of Ran, cargos still explore the entire volume of the NPC, but have a dramatically reduced probability of exit into the nucleus from the pore, suggesting that NPC entry and exit steps are not equivalent and that the pore is functionally asymmetric to importing cargos.