Abstract
Synaptic ribbons are presynaptic specializations that define eponymous ribbon synapses. Synaptic ribbons are largely composed of RIBEYE, a protein containing an N-terminal A-domain and a carboxyterminal B-domain that is identical with CtBP2, a NAD(H)-binding transcriptional co-repressor. Previously we showed that synaptic ribbons are completely absent in RIBEYE knockout mice in which the RIBEYE A-domain-encoding exon had been deleted, but CtBP2 is still made, demonstrating that the A-domain is required for synaptic ribbon assembly. In the present study, we asked whether the RIBEYE B-domain also has an essential role in the assembly of synaptic ribbons. For this purpose, we made use of RIBEYE knockin mice in which the RIBEYE B-domain was replaced by a fluorescent protein domain, whereas the RIBEYE A-domain was retained unchanged. We found that replacing the RIBEYE B-domain with a fluorescent protein module destabilizes the resulting hybrid protein and causes a complete loss of synaptic ribbons. Our results thus demonstrate an essential role of the RIBEYE B-domain in enabling RIBEYE assembly into synaptic ribbons, reinforcing the notion that RIBEYE is the central organizer of synaptic ribbons.
Highlights
Ribbon synapses are specialized chemical synapses found in the retina, inner ear, and pineal gland (Matthews and Fuchs, 2010; Moser et al, 2020)
We analyzed RIBEYE knockin (KI) mice, RBEKI (Maxeiner et al, 2016) to study whether RIBEYE B-domain has a role in the assembly of synaptic ribbons
By applying quantitative 3D SR-SIM analyses, we found that the contour length of synaptic ribbons was smaller in heterozygous RBEWT/KI compared to RBEWT/WT mice
Summary
Ribbon synapses are specialized chemical synapses found in the retina, inner ear, and pineal gland (Matthews and Fuchs, 2010; Moser et al, 2020). RIBEYE B-Domain Is Essential for Assembly of Synaptic Ribbons determines the pool size of ribbon-associated vesicles (Moser et al, 2020; Kesharwani et al, 2021). Rod photoreceptor synapses are built in a fairly uniform manner They contain a single, large active zone with a single large, horseshoe-shaped synaptic ribbon (Schmitz, 2009; Moser et al, 2020). Bipolar cell terminals possess multiple active zones with smaller synaptic ribbons that are morphologically and functionally more diverse than rod photoreceptor synapses in the outer retina (Moser et al, 2020). The RIBEYE B-domain is essential for the assembly of synaptic ribbons
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