Abstract

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.

Highlights

  • Vesicular exocytosis, involving either synaptic vesicles (SVs; [1,2,3]) or secretory exosomes [4,5,6,7] is essential for neuronal function

  • Some of the putative proteins involved in tethering near active zone (AZ) membrane consists of RIM2α, bassoon, complexin3/4, and the hair cell-specific protein otoferlin

  • SV docking at inner hair cell (IHC) ribbon synapses seems to operate without the neuronal sensitive factor attachment protein receptor (SNARE), implicating an alternative docking and priming mechanism, which is distinct from that of the neuronal synapses

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Summary

Introduction

Vesicular exocytosis, involving either synaptic vesicles (SVs; [1,2,3]) or secretory exosomes [4,5,6,7] is essential for neuronal function. They are found in lower vertebrate pinealocytes in the pineal gland [72], fish lateral lines [73,74], and electroreceptors [75,76], as well as in frog saccular or turtle [77,78] hair cells They all share a structural specialization appearing as a large electron-dense projection, the synaptic ribbon, which can reach in the photoreceptor a size of several hundreds of nanometers, and this way is capable to cluster a large number of SVs [71,79,80].

Synaptic Vesicle Pool Organization at Synapses
Interconnectors in Neuronal Synapses form a Network of SVs
SV Tethering in Membrane-Proximity
10. SV Docking and Priming at Neuronal Synapses
11. Synaptic Vesicle Tethering at the AZ Membrane of Ribbon Synapses Recruit SVs
12. Potential Components of SV Tethers at IHC Ribbon Synapses
13. Synaptic Vesicle Docking at Ribbon Synapses
Findings
14. Conclusions

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