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 Ca2+‐buffer EGTA, suggesting that synaptic ribbons mediate nano‐domain coupling of Ca2+ 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 Ca2+ channels.
The synaptic ribbon is a large proteinaceous structure found in photoreceptor synapses that is specialized for fast and sustained synaptic vesicle exocytosis. RIBEYE is the only known ribbon‐specific protein thought to be an essential part in the organization of the synaptic ribbon.
Deletion of RIBEYE results in complete loss of all synaptic ribbons found in photoreceptors and rod bipolar cells.
Absence of the synaptic ribbon reduces the number of docked and membrane‐close vesicles at the presynaptic active zone but not the number of vesicles in the reserve pool.
Ablation of synaptic ribbons by the RIBEYE KO causes a loss of fast and sustained neurotransmitter release at the rod bipolar cell/AII amacrine cell synapse.
Nano‐domain coupling of synaptic release sites with presynaptic voltage‐gated Ca2+ channels (Cav1.4 channels) is distorted in RIBEYE knockout mice.
- Received August 2, 2015.
- Revision received December 31, 2015.
- Accepted February 1, 2016.
- © 2016 The Authors
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