Biology Seminar - Jennifer Lippincott-Schwartz

Title: From muscle to memory: role of periodic ER-plasma membrane junctions in supporting long-range Ca2+ signal integration in dendrites

Abstract:

Neuronal dendrites relay synaptic inputs over long distances by voltage-dependent and independent propagation. Here, I describe a system of periodically arranged endoplasmic reticulum-plasma membrane (ER-PM) junctions that play a role in activity-evoked intracellular signals propagation in dendrites. The ER-PM junctions tiled the PM 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 ryanodine receptors Ca2+-release channel, we show that ER-PM junctions serve as 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.