Ribbon Synapses and Retinal Disease: Review

Frederick, Courtney; Zenisek, David

doi:10.3390/ijms24065090

Cited by 10 publications

(9 citation statements)

References 122 publications

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“…Therefore, we focused on the localization of RC3α/DMXL2 in photoreceptor synapses of the OPL. Photoreceptor synapses in the mouse retina are predominantly rod photoreceptors synapses [ 7 , 70 ]. Rod photoreceptor synapses typically possess a single, large active zone with a single and large horseshoe-shaped synaptic ribbon [ 7 , 70 ].…”

Section: Resultsmentioning

confidence: 99%

“…Photoreceptor synapses in the mouse retina are predominantly rod photoreceptors synapses [ 7 , 70 ]. Rod photoreceptor synapses typically possess a single, large active zone with a single and large horseshoe-shaped synaptic ribbon [ 7 , 70 ]. The entire presynaptic terminal is filled with many highly motile synaptic vesicles that can bind to the synaptic ribbon [ 71 ].…”

Section: Resultsmentioning

confidence: 99%

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Rabconnectin-3α/DMXL2 Is Locally Enriched at the Synaptic Ribbon of Rod Photoreceptor Synapses

Dittrich

Ramesh

Jung

et al. 2023

Cells

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Ribbon synapses reliably transmit synaptic signals over a broad signalling range. Rod photoreceptor ribbon synapses are capable of transmitting signals generated by the absorption of single photons. The high precision of ribbon synapses emphasizes the need for particularly efficient signalling mechanisms. Synaptic ribbons are presynaptic specializations of ribbon synapses and are anchored to the active zone. Synaptic ribbons bind many synaptic vesicles that are delivered to the active zone for continuous and faithful signalling. In the present study we demonstrate with independent antibodies at the light- and electron microscopic level that rabconnectin-3α (RC3α)—alternative name Dmx-like 2 (DMXL2)—is localized to the synaptic ribbons of rod photoreceptor synapses in the mouse retina. In the brain, RC3α-containing complexes are known to interact with important components of synaptic vesicles, including Rab3-activating/inactivating enzymes, priming proteins and the vesicular H+-ATPase that acidifies the synaptic vesicle lumen to promote full neurotransmitter loading. The association of RC3α/DMXL2 with rod synaptic ribbons of the mouse retina could enable these structures to deliver only fully signalling-competent synaptic vesicles to the active zone thus contributing to reliable synaptic communication.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Rabconnectin-3α/DMXL2 Is Locally Enriched at the Synaptic Ribbon of Rod Photoreceptor Synapses

Dittrich

Ramesh

Jung

et al. 2023

Cells

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“…Latency to find the platform was manually recorded and confirmed using recorded videos. Male and female mice were tested separately, and no sex differences in performance were identified post-hoc using two-way RM-ANOVA (Supplementary Table 1 WT (4) G369i KI (5) Ca V 1.4 KO (5)…”

Section: Visible Platform Swim Testmentioning

confidence: 99%

“…As shown for rod synapses 19 , ribbons and other components of the pre-and post-synaptic complex assemble normally at cone synapses in G369i mice (Figs. 1,4,5).…”

Section: A Non-canonical Role For Cav14 In Regulating Cone Synapse As...mentioning

confidence: 99%

A non-conducting role of the Ca_v1.4 Ca²⁺channel drives homeostatic plasticity at the cone photoreceptor synapse

Maddox,

Ordemann,

de la Rosa Vázquez

et al. 2023

Preprint

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In congenital stationary night blindness type 2 (CSNB2)—a disorder involving dysfunction of the Cav1.4 Ca2+channel—visual impairment is relatively mild considering that Cav1.4 mediates synaptic transmission by rod and cone photoreceptors. Here, we addressed this conundrum using a Cav1.4 knockout (KO) mouse and a knock-in (KI) mouse expressing a non-conducting Cav1.4 mutant. Surprisingly, aberrant Cav3 currents were detected in cones of the KI and KO but not wild-type mice. Cone synapses, which fail to develop in KO mice, are present but enlarged in KI mice. Moreover, light responses in cone pathways and photopic visual behavior are preserved in KI but not in KO mice. In CSNB2, we propose that Cav3 channels maintain cone synaptic output provided that the Ca2+-independent role of Cav1.4 in cone synaptogenesis remains intact. Our findings reveal an unexpected form of homeostatic plasticity that relies on a non-canonical role of an ion channel.

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“…The inner ear and retina contain sensory cells that rely on specialized ribbon synapses that faithfully transmit the timing, duration, and intensity of sensory stimuli to the brain. Ribbon synapses are critical for human hearing and vision–disruption of these synapses is linked to auditory and visual disorders (Frederick and Zenisek, 2023; Kujawa and Liberman, 2015). The hallmark feature of these synapses is a presynaptic specialization called a ribbon, which is a dense body made up primarily of the protein Ribeye (Schmitz et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Microtubule networks in zebrafish hair cells facilitate presynapse transport and fusion during development

Hussain,

Pinter,

Uhl

et al. 2024

Preprint

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Sensory cells in the retina and inner ear rely on specialized ribbon synapses for neurotransmission. Disruption of these synapses is linked to visual and auditory dysfunction, but it is unclear how these unique synapses are formed. Ribbon synapses are defined by a presynaptic density called a ribbon. Using live-imaging approaches in zebrafish, we find that early in hair-cell development, many small ribbon precursors are present throughout the cell. Later in development, fewer and larger ribbons remain, and localize at the presynaptic active zone (AZ). Using tracking analyses, we show that ribbon precursors exhibit directed motion along an organized microtubule network towards the presynaptic AZ. In addition, we show that ribbon precursors can fuse together on microtubules to form larger ribbons. Using pharmacology, we find that microtubule disruption interferes with ribbon motion, fusion, and normal synapse formation. Overall, this work demonstrates a dynamic series of events that underlies formation of a critical synapse required for sensory function.

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Ribbon Synapses and Retinal Disease: Review

Cited by 10 publications

References 122 publications

Rabconnectin-3α/DMXL2 Is Locally Enriched at the Synaptic Ribbon of Rod Photoreceptor Synapses

Rabconnectin-3α/DMXL2 Is Locally Enriched at the Synaptic Ribbon of Rod Photoreceptor Synapses

A non-conducting role of the Ca_v1.4 Ca²⁺channel drives homeostatic plasticity at the cone photoreceptor synapse

Microtubule networks in zebrafish hair cells facilitate presynapse transport and fusion during development

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Ribbon Synapses and Retinal Disease: Review

Cited by 10 publications

References 122 publications

Rabconnectin-3α/DMXL2 Is Locally Enriched at the Synaptic Ribbon of Rod Photoreceptor Synapses

Rabconnectin-3α/DMXL2 Is Locally Enriched at the Synaptic Ribbon of Rod Photoreceptor Synapses

A non-conducting role of the Cav1.4 Ca2+channel drives homeostatic plasticity at the cone photoreceptor synapse

Microtubule networks in zebrafish hair cells facilitate presynapse transport and fusion during development

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A non-conducting role of the Ca_v1.4 Ca²⁺channel drives homeostatic plasticity at the cone photoreceptor synapse