Journal Article Ppublish 7 citations
PubMed: 39708809 DOI: 10.1016/j.cell.2024.11.029
Periodic ER-plasma membrane junctions support long-range Ca signal integration in dendrites.
Cell 188(2):484-500.e22
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, Jennifer Lippincott-Schwartz
Affiliations
- HHMI Janelia Research Campus, Ashburn, VA 20147, USA.
- Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA.
- Yale School of Medicine, New Haven, CT 06510, USA.
- Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06510, USA.
- Department of Neuroscience, Department of Cell Biology, Program in Cellular Neuroscience Neurodegeneration and Repair, Howard Hughes Medical Institute, New Haven, CT 06510, USA.
- HHMI Janelia Research Campus, Ashburn, VA 20147, USA; Weill Cornell Medicine, Department of Biochemistry, New York, NY 10065, USA.
- HHMI Janelia Research Campus, Ashburn, VA 20147, USA.
Abstract
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 Ca channels and ER Ca-release channels (ryanodine receptors), ER-PM junctions are hubs for ER-PM crosstalk, fine-tuning of Ca homeostasis, and local activation of the Ca/calmodulin-dependent protein kinase II. Local spine stimulation activates the Ca modulatory machinery, facilitating signal transmission and ryanodine-receptor-dependent Ca release at ER-PM junctions over 20 μm away. Thus, interconnected ER-PM junctions support signal propagation and Ca 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.
MeSH
Cell Membrane, Ryanodine, Endoplasmic Reticulum, Membranes, Plasma, Dendrites, Volume Electron Microscopy, Spine
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