Neuroscience

Membrane

Biology

Biophysics

Membrane protein

Hippocampal formation

Endoplasmic reticulum

Unfolded protein response

Chemistry

Cell membrane

Cell biology

Biochemistry

Potassium channel

Proceedings of the National Academy of Sciences

Significance In addition to functioning as a delayed-rectifier K + channel, Kv2.1 interacts with the cortical endoplasmic reticulum (ER) in hippocampal neurons to form somatic ER/plasma membrane (ER/PM) junctions. Neuronal activity and insult induce Kv2.1 release from the cortical ER and subsequent ER withdrawal from the PM. Neuronal ER/PM contacts represent &gt;10% of the cell surface and play roles in membrane trafficking, the regulation of burst firing, Ca 2+ homeostasis, and control of PM lipid. We report here that Kv2 channel–VAMP-associated protein (VAP) interaction tethers the cortical ER to the PM via a noncanonical FFAT motif contained within the channel C terminus. Since VAPs have a wide-ranging interactome, Kv2-induced ER remodeling and VAP concentration at ER/PM contacts likely play a central role in neuronal physiology.

Kv2 potassium channels form endoplasmic reticulum/plasma membrane junctions via interaction with VAPA and VAPB