Periodic ER-plasma membrane junctions support long-range Ca2+signal integration in dendrites

Abstract

SummaryNeuronal dendrites must relay synaptic inputs over long distances, but the mechanisms by which activity-evoked intracellular signals propagate over macroscopic distances remain unclear. Here, we discovered a system of periodically arranged endoplasmic reticulum-plasma membrane (ER-PM) junctions tiling the plasma membrane of dendrites at ∼1 μm intervals, interlinked by a meshwork of ER tubules patterned in a ladder-like array. Populated with Junctophilin-linked plasma membrane voltage-gated Ca2+channels and ER Ca2+-release channels (ryanodine receptors), ER-PM junctions are hubs for ER-PM crosstalk, fine-tuning of Ca2+homeostasis, and local activation of the Ca2+/calmodulin-dependent protein kinase II. Local spine stimulation activates the Ca2+modulatory machinery facilitating voltage-independent signal transmission and ryanodine receptor-dependent Ca2+release at ER-PM junctions over 20 μm away. Thus, interconnected ER-PM junctions support signal propagation and Ca2+release from the spine-adjacent ER. The capacity of this subcellular architecture to modify both local and distant membrane-proximal biochemistry potentially contributes to dendritic computations.HighlightsPeriodic ER-PM junctions tile neuronal dendritic plasma membrane in rodent and fly.ER-PM junctions are populated by ER tethering and Ca2+release and influx machinery.ER-PM junctions act as sites for local activation of CaMKII.Local spine activation drives Ca2+release from RyRs at ER-PM junctions over 20 μm.