Department of Membrane Biochemistry, Institute of Chemistry and Biochemistry, Freie Universität and Charité-Universitätsmedizin, Berlin, Germany.
Biochem Soc Trans. 2010 Feb;38(Pt 1):181-6. doi: 10.1042/BST0380181.
During neurotransmitter release, SVs (synaptic vesicles) fuse at the active zone and are recovered predominantly via clathrin-mediated endocytosis at the presynaptic compartment surrounding the site of release, referred to as the periactive zone. Exo- and endo-cytosis in synapses are tightly temporarily and spatially coupled to sustain synaptic transmission. The molecular mechanisms linking these two cellular events, which take place in separate compartments of the nerve terminal, remain largely enigmatic. Several lines of evidence indicate that multiple factors may be involved in exocytic-endocytic coupling including SV integral membrane proteins, SV membrane lipids and the membrane-associated actin cytoskeleton. A number of recent studies also indicate that multimodular adaptor proteins shuttling between the active and periactive zones aid the dynamic assembly of macromolecular protein complexes that execute the exo- and endo-cytic limbs of the SV cycle. Here, we discuss recent evidence implicating the multidomain scaffolding and adaptor protein ITSN1 (intersectin 1) as a central regulator of SV cycling.
在神经递质释放过程中，SV（突触小泡）在活性区融合，并主要通过网格蛋白介导的内吞作用在释放部位周围的突触前区室中回收，称为活性区周围区室。突触中外排和内吞作用与维持突触传递紧密地在时间和空间上偶联。将这两个发生在神经末梢不同隔室中的细胞事件联系起来的分子机制在很大程度上仍然是个谜。有几条证据表明，多种因素可能参与到胞吐-胞吞偶联中，包括 SV 整合膜蛋白、SV 膜脂质和膜相关的肌动蛋白细胞骨架。最近的一些研究还表明，穿梭于活性区和活性区周围区室之间的多模块衔接蛋白有助于执行 SV 循环的胞吐和胞吞作用的大分子蛋白复合物的动态组装。在这里，我们讨论了最近的证据，表明多域支架和衔接蛋白 ITSN1（衔接蛋白 1）是 SV 循环的中央调节因子。
