The Making of Synaptic Ribbons: How They Are Built and What They Do

Ribbon synapses in the retina and inner ear maintain tonic neurotransmitter release at high rates to transduce a broad bandwidth of stimulus intensities. In ribbon synapses, synaptic vesicles can be released by a slow, sustained mode and by fast, synchronous mechanisms. The high release rates require structural and functional specializations. The synaptic ribbon is the key structural specialization of ribbon synapses. Synaptic ribbons are large, electron-dense structures that immobilize numerous synaptic vesicles next to presynaptic release sites. A main component of synaptic ribbons is the protein RIBEYE that has the capability to build the scaffold of the synaptic ribbon via multiple RIBEYE-RIBEYE interactions. A modular assembly model of synaptic ribbons has been proposed in which synaptic ribbons are formed from individual RIBEYE subunits. The scaffold of the synaptic ribbon provides a docking site for RIBEYE-associated proteins that could execute specific synaptic ribbon functions. Multiple functions have been assigned to synaptic ribbons including roles in exocytosis, endocytosis, and synaptic membrane trafficking. Recent studies demonstrated the importance of synaptic ribbons for fast, synchronous release and emphasized the need of a tight and efficient coupling between presynaptic Ca²⁺ signaling and exocytosis. The present review summarizes recent advances on structure and function of synaptic ribbons.