周期性内质膜结支持远程Ca2+信号在树突中的整合

IF 45.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Cell Pub Date : 2024-12-20 DOI:10.1016/j.cell.2024.11.029
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
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引用次数: 0

摘要

神经元树突必须长距离传递突触输入,但活动诱发的细胞内信号在宏观距离上传播的机制尚不清楚。在这里,我们发现了一个周期性排列的内质网-质膜(ER- pm)连接系统,以~ 1 μm的间隔铺在树突的质膜上,通过以阶梯状阵列图案排列的ER小管网络相互连接。ER- pm连接由连接蛋白连接的质膜电压门控Ca2+通道和ER Ca2+释放通道(ryanodine受体)组成,是ER- pm串扰、Ca2+稳态微调和Ca2+/钙调素依赖性蛋白激酶II局部激活的枢纽。局部脊柱刺激激活Ca2+调节机制,促进20 μm外ER-PM连接处的信号传递和ryanoine -受体依赖性Ca2+释放。因此,相互连接的ER- pm连接支持信号传播和来自脊柱邻近ER的Ca2+释放。这种亚细胞结构改变局部和远处膜近端生物化学的能力可能有助于树突计算。
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Periodic ER-plasma membrane junctions support long-range Ca2+ signal integration in dendrites
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.
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来源期刊
Cell
Cell 生物-生化与分子生物学
CiteScore
110.00
自引率
0.80%
发文量
396
审稿时长
2 months
期刊介绍: Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.
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