Figure 3.

Model of the Kv2.1-induced ER/PM junction. Calcineurin-dependent dephosphorylation of the Kv2.1 C-terminus results in release from the ER VAPs, Kv2.1 declustering, loss of the ER/PM junction, VAP redistribution, and cortical ER retraction. The clustered Kv2.1 channels are proposed to be non-conducting under resting conditions [37]. Both the Kv2.1-containing and Kv2.1-free ER/PM junctions are trafficking hubs where dense core vesicle exocytosis [14,15] and membrane protein delivery is concentrated [44], perhaps in part due to these membrane contact sites residing in, or forming, “holes” in the cortical actin [36]. However, Kv2.1-containing membrane junctions are proposed to also concentrate SNARE proteins, for Kv2.1 contains VAMP-2, SNAP25 and syntaxin binding domains [72–74].