Maxeiner Stephan, Luo Fujun, Tan Alison, Schmitz Frank, Südhof Thomas C
Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute Stanford University School of Medicine, Stanford, CA, USA Department of Neuroanatomy, Institute for Anatomy and Cell Biology Medical School Saarland University, Homburg/Saar, Germany.
Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute Stanford University School of Medicine, Stanford, CA, USA.
EMBO J. 2016 May 17;35(10):1098-114. doi: 10.15252/embj.201592701. Epub 2016 Feb 29.
Synaptic ribbons are large proteinaceous scaffolds at the active zone of ribbon synapses that are specialized for rapid sustained synaptic vesicles exocytosis. A single ribbon-specific protein is known, RIBEYE, suggesting that ribbons may be constructed from RIBEYE protein. RIBEYE knockdown in zebrafish, however, only reduced but did not eliminate ribbons, indicating a more ancillary role. Here, we show in mice that full deletion of RIBEYE abolishes all presynaptic ribbons in retina synapses. Using paired recordings in acute retina slices, we demonstrate that deletion of RIBEYE severely impaired fast and sustained neurotransmitter release at bipolar neuron/AII amacrine cell synapses and rendered spontaneous miniature release sensitive to the slow Ca(2+)-buffer EGTA, suggesting that synaptic ribbons mediate nano-domain coupling of Ca(2+) channels to synaptic vesicle exocytosis. Our results show that RIBEYE is essential for synaptic ribbons as such, and may organize presynaptic nano-domains that position release-ready synaptic vesicles adjacent to Ca(2+) channels.
突触带是带状突触活性区的大型蛋白质支架，专门用于快速持续的突触小泡胞吐作用。已知一种单一的带状特异性蛋白质，即视网膜带状蛋白（RIBEYE），这表明突触带可能由RIBEYE蛋白构成。然而，在斑马鱼中敲低RIBEYE仅减少了突触带，但并未消除，这表明其作用更为辅助。在这里，我们在小鼠中表明，完全缺失RIBEYE会消除视网膜突触中的所有突触前突触带。利用急性视网膜切片中的配对记录，我们证明缺失RIBEYE会严重损害双极神经元/AII无长突细胞突触处快速且持续的神经递质释放，并使自发微小释放对缓慢的Ca(2+)缓冲剂乙二醇双四乙酸（EGTA）敏感，这表明突触带介导了Ca(2+)通道与突触小泡胞吐作用的纳米域偶联。我们的结果表明，RIBEYE本身对于突触带至关重要，并且可能组织突触前纳米域，使准备释放的突触小泡定位在Ca(2+)通道附近。
