担当：基盤研・山澤先生
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Cell . 2025 Jan 23;188(2):484-500.e22.
Periodic ER-plasma membrane junctions support long-range Ca2+ signal integration in dendrites
Lorena Benedetti 1 , Ruolin Fan 2 , Aubrey V Weigel 1 , Andrew S Moore 1 , Patrick R Houlihan 1 , Mark Kittisopikul 1 , Grace Park 1 , Alyson Petruncio 1 , Philip M Hubbard 1 , Song Pang 3 , C Shan Xu 4 , Harald F Hess 1 , Stephan Saalfeld 1 , Vidhya Rangaraju 2 , David E Clapham 1 , Pietro De Camilli 5 , Timothy A Ryan 6 , Jennifer Lippincott-Schwartz 7
Affiliations
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 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.
Keywords: Ca(2+)/calmodulin-dependent protein kinase II; CaMKII; Drosophila melanogaster; ER-PM junctions; Junctophilin; RyRs; VGCC; endoplasmic reticulum; hippocampal neurons; ryanodine receptors; voltage-gated calcium channels; volume electron microscopy.