美国约翰霍普金斯大学医学院Shigeki Watanabe研究小组取得一项新突破。他们研制了交叉蛋白和亲内蛋白凝聚主要突触囊泡释放位点补充。该项研究成果发表在2025年7月8日出版的《自然—神经科学》上。

本研究发现，在无主题海马兴奋性突触中，替代囊泡被交叉蛋白-1聚集在释放位点所在的活跃区附近。具体来说，相交素-1与亲内蛋白A1形成动态分子凝聚，并在该区域周围封存囊泡。在缺乏交叉蛋白1的情况下，质膜20纳米范围内的聚集小泡数量减少，空出的位点不能迅速补充，导致突触抑制。破坏亲内蛋白A1结合的交叉蛋白-1突变导致类似的表型。在缺乏亲内蛋白A1的情况下，交叉蛋白1定位错误，囊泡的替代池无法进入，这表明需要亲内蛋白A1来动员这些囊泡。他们的工作描述了突触内的替代区域，在那里储存替代囊泡以补充释放部位。

研究人员表示，突触囊泡脱落后，空出的释放位点立即被新的囊泡补充，用于随后的神经传递。假设这些替代囊泡位于释放点附近，并且是偶然的主题。

附：英文原文

Title: Intersectin and endophilin condensates prime synaptic vesicles for release site replenishment

Author: Ogunmowo, Tyler H., Hoffmann, Christian, Patel, Chintan, Pepper, Renee, Wang, Han, Gowrisankaran, Sindhuja, Idel, Johanna, Ho, Annie, Raychaudhuri, Sumana, Maher, Brady J., Cooper, Benjamin H., Milosevic, Ira, Milovanovic, Dragomir, Watanabe, Shigeki

Issue&Volume: 2025-07-08

Abstract: Following synaptic vesicle fusion, vacated release sites are replenished immediately by new vesicles for subsequent neurotransmission. These replacement vesicles are assumed to be located near release sites and used by chance. Here we find in mouse hippocampal excitatory synapses that replacement vesicles are clustered near the active zone where release sites reside by intersectin-1. Specifically, intersectin-1 forms dynamic molecular condensates with endophilin A1 and sequesters vesicles around this region. In the absence of intersectin-1, fewer vesicles cluster within 20nm of the plasma membrane, and consequently vacated sites cannot be replenished rapidly, leading to synaptic depression. Mutations in intersectin-1 that disrupt endophilin A1 binding result in similar phenotypes. In the absence of endophilin A1, intersectin-1 is mislocalized, and this replacement pool of vesicles cannot be accessed, suggesting that endophilin A1 is needed to mobilize these vesicles. Thus, our work describes the replacement zone within a synapse, where replacement vesicles are stored for replenishment of the release site.

DOI: 10.1038/s41593-025-02002-4

Source: https://www.nature.com/articles/s41593-025-02002-4