E-Syt1 Regulates Neuronal Activity-Dependent Endoplasmic Reticulum–Plasma Membrane Junctions and Surface Expression of AMPA Receptors

Abstract

Endoplasmic reticulum (ER)–plasma membrane (PM) contact sites/junctions play important roles in cell physiology including signal transduction, ion and lipid transfer, and membrane dynamics. However, little is known about the dynamic regulation and functional roles of ER–PM junctions in neurons. Using a split green fluorescent protein-based membrane contact probe, we find that the density of ER–PM contact sites changes dynamically in the dendrites of hippocampal neurons undergoing long-term synaptic potentiation (LTP). We show that the Ca2±-sensing membrane tethering protein Extended Synaptotagmin 1 (E-Syt1) mediates the formation of ER–PM contact sites during LTP. We also show that E-Syt1 is required for neuronal activity-dependent surface expression of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-type glutamate receptors. These findings implicate ER–PM junctions in the regulation of neurotransmitter receptor trafficking and synaptic plasticity.