担当：基盤研・山澤先生

いつも大変お世話になっております。

4月16日は下記の論文を紹介させて頂きます。

宜しくお願い申し上げます。

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.