Molecular Architecture of Synapses Group, Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, 37075 Göttingen, Germany.
Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, 37075 Göttingen, Germany.
Int J Mol Sci. 2019 Apr 30;20(9):2147. doi: 10.3390/ijms20092147.
A critical aim in neuroscience is to obtain a comprehensive view of how regulated neurotransmission is achieved. Our current understanding of synapses relies mainly on data from electrophysiological recordings, imaging, and molecular biology. Based on these methodologies, proteins involved in a synaptic vesicle (SV) formation, mobility, and fusion at the active zone (AZ) membrane have been identified. In the last decade, electron tomography (ET) combined with a rapid freezing immobilization of neuronal samples opened a window for understanding the structural machinery with the highest spatial resolution in situ. ET provides significant insights into the molecular architecture of the AZ and the organelles within the presynaptic nerve terminal. The specialized sensory ribbon synapses exhibit a distinct architecture from neuronal synapses due to the presence of the electron-dense synaptic ribbon. However, both synapse types share the filamentous structures, also commonly termed as tethers that are proposed to contribute to different steps of SV recruitment and exocytosis. In this review, we discuss the emerging views on the role of filamentous structures in SV exocytosis gained from ultrastructural studies of excitatory, mainly central neuronal compared to ribbon-type synapses with a focus on inner hair cell (IHC) ribbon synapses. Moreover, we will speculate on the molecular entities that may be involved in filament formation and hence play a crucial role in the SV cycle.
神经科学的一个关键目标是全面了解调节性神经递质传递是如何实现的。我们目前对突触的理解主要依赖于来自电生理学记录、成像和分子生物学的数据。基于这些方法，已经确定了参与突触小泡 (SV) 在活性区 (AZ) 膜处形成、迁移和融合的蛋白质。在过去的十年中，电子断层扫描 (ET) 与神经元样本的快速冷冻固定相结合，为理解具有最高空间分辨率的 AZ 结构机制开辟了一扇窗口。ET 为 AZ 内的分子结构和细胞器提供了重要的见解。由于存在电子致密的突触带，特殊的感觉带状突触与神经元突触具有不同的结构。然而，这两种突触类型都具有丝状结构，也通常称为系绳，据推测，这些结构有助于 SV 募集和胞吐作用的不同步骤。在这篇综述中，我们讨论了从兴奋性突触（主要是中枢神经元）的超微结构研究中获得的丝状结构在 SV 胞吐作用中的作用的新观点，与带状型突触相比，重点放在内毛细胞 (IHC) 带状突触上。此外，我们将推测可能参与丝状形成并因此在 SV 循环中发挥关键作用的分子实体。
