Kavli Affiliate: Timothy A. Ryan and Pietro De Camilli;
| Authors: Lorena Benedetti, Ruolin Fan, Aubrey V. Weigel, Andrew S. Moore, Patrick R. Houlihan, Mark Kittisopikul, Grace Park, Alyson Petruncio, Philip M. Hubbard, Song Pang, C. Shan Xu, Harald F. Hess, Stephan Saalfeld, Vidhya Rangaraju, David E. Clapham, Pietro De Camilli, Timothy A. Ryan and Jennifer Lippincott-Schwartz
| Summary:
Neuronal 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.