L- type Ca2+ channel activation of STIM1-Orai1 signaling remodels the dendritic spine ER to maintain long- term structural plasticity

• 成果类型: Article
• 署名作者: Dittmer, Philip J.; Dell'Acqua, Mark L.
• 署名单位: University of Colorado System; University of Colorado Anschutz Medical Campus
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14401
• DOI: 10.1073/pnas.2407324121
• 发表日期: 2024-08-27
• 关键词: ampa receptor trafficking; operated calcium-entry; endoplasmic-reticulum; release; potentiation; DEPRESSION; ca1; ORGANIZATION; hippocampus; components

摘要

Learning and memory require coordinated structural and functional plasticity at neuronal glutamatergic synapses located on dendritic spines. Here, we investigated how the endoplasmic reticulum (ER) controls postsynaptic Ca2+ signaling and long- term potentiation of dendritic spine size, i.e., sLTP that accompanies functional strengthening of glutamatergic synaptic transmission. In most ER- containing (ER+) spines, high- frequency optical glutamate uncaging (HFGU) induced long- lasting sLTP that was accompanied by a persistent increase in spine ER content downstream of a signaling (LTCCs), and Orai1 channels, the latter being activated by stromal interaction molecule (ER-) spines expressed only transient sLTP and exhibited weaker Ca2+ signals noticeably lacking Orai1 and ER contributions. Consistent with spine ER regulating structural metaplasticity, delivery of a second stimulus to ER- spines induced ER recruitment along with persistent sLTP, whereas ER+ spines showed no additional increases in size or ER content in response to sequential stimulation. Surprisingly, the physical interaction between STIM1 and Orai1 induced by ER Ca2+ release, but not the resulting Ca2+ entry through Orai1 channels, proved necessary for the persistent increases in both spine size and ER content required for expression of long- lasting late sLTP.