Photoreceptor Compartment-Specific TULP1 Interactomes

Ebke, Lindsey A.; Sinha, Satyabrata; Pauer, Gayle J.; Hagstrom, Stephanie A.

doi:10.3390/ijms22158066

Cited by 4 publications

(3 citation statements)

References 68 publications

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“…Interestingly, several other proteins also share a dual localization at the photoreceptor cilium and the photoreceptor synaptic ribbon. These include the PIP 2 -binding tubby-like protein 1 (Tulp1) that is present both at the photoreceptor synaptic ribbon complex [52][53][54] and the photoreceptor cilium [52,54]. The same dual localization, i.e., at the cilium and the ribbon, has been also described for the kinesin-2 motor protein Kif3a [55][56][57][58][59].…”

Section: Discussionmentioning

confidence: 94%

Ciliary Proteins Repurposed by the Synaptic Ribbon: Trafficking Myristoylated Proteins at Rod Photoreceptor Synapses

Suiwal

Dembla

Schwarz

et al. 2022

IJMS

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The Unc119 protein mediates transport of myristoylated proteins to the photoreceptor outer segment, a specialized primary cilium. This transport activity is regulated by the GTPase Arl3 as well as by Arl13b and Rp2 that control Arl3 activation/inactivation. Interestingly, Unc119 is also enriched in photoreceptor synapses and can bind to RIBEYE, the main component of synaptic ribbons. In the present study, we analyzed whether the known regulatory proteins, that control the Unc119-dependent myristoylated protein transport at the primary cilium, are also present at the photoreceptor synaptic ribbon complex by using high-resolution immunofluorescence and immunogold electron microscopy. We found Arl3 and Arl13b to be enriched at the synaptic ribbon whereas Rp2 was predominantly found on vesicles distributed within the entire terminal. These findings indicate that the synaptic ribbon could be involved in the discharge of Unc119-bound lipid-modified proteins. In agreement with this hypothesis, we found Nphp3 (Nephrocystin-3), a myristoylated, Unc119-dependent cargo protein enriched at the basal portion of the ribbon in close vicinity to the active zone. Mutations in Nphp3 are known to be associated with Senior–Løken Syndrome 3 (SLS3). Visual impairment and blindness in SLS3 might thus not only result from ciliary dysfunctions but also from malfunctions of the photoreceptor synapse.

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Section: Discussionmentioning

confidence: 94%

Ciliary Proteins Repurposed by the Synaptic Ribbon: Trafficking Myristoylated Proteins at Rod Photoreceptor Synapses

Suiwal

Dembla

Schwarz

et al. 2022

IJMS

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“…Horizontal ("retinal layer-wise") cryo-sectioning of the mouse retina was performed similarly as previously described [81,82]. For sectioning of horizontal cryo-sections that contained photoreceptors free of the inner retinal layers, eyes from Cre-positive, tau-GFP heterozygous mice were enucleated within 5 min post-mortem.…”

Section: Horizontal Cryo-sectioning Of the Mouse Retinamentioning

confidence: 99%

A Novel Cre Recombinase Mouse Strain for Cell-Specific Deletion of Floxed Genes in Ribbon Synapse-Forming Retinal Neurons

Suiwal,

Wartenberg,

Boehm

et al. 2024

IJMS

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We generated a novel Cre mouse strain for cell-specific deletion of floxed genes in ribbon synapse-forming retinal neurons. Previous studies have shown that the RIBEYE promotor targets the expression of recombinant proteins such as fluorescently tagged RIBEYE to photoreceptors and retinal bipolar cells and generates fluorescent synaptic ribbons in situ in these neurons. Here, we used the same promotor to generate a novel transgenic mouse strain in which the RIBEYE promotor controls the expression of a Cre-ER(T2) recombinase (RIBEYE-Cre). To visualize Cre expression, the RIBEYE-Cre animals were crossed with ROSA26 tau-GFP (R26-τGFP) reporter mice. In the resulting RIBEYE-Cre/R26 τGFP animals, Cre-mediated removal of a transcriptional STOP cassette results in the expression of green fluorescent tau protein (tau-GFP) that binds to cellular microtubules. We detected robust tau-GFP expression in retinal bipolar cells. Surprisingly, we did not find fluorescent tau-GFP expression in mouse photoreceptors. The lack of tau-GFP reporter protein in these cells could be based on the previously reported absence of tau protein in mouse photoreceptors which could lead to the degradation of the recombinant tau protein. Consistent with this, we detected Cre and tau-GFP mRNA in mouse photoreceptor slices by RT-PCR. The transgenic RIBEYE-Cre mouse strain provides a new tool to study the deletion of floxed genes in ribbon synapse-forming neurons of the retina and will also allow for analyzing gene deletions that are lethal if globally deleted in neurons.

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“…Further, the mouse demonstrated synaptic disruption [ 64 ]. At the ribbon synapse, tubby-like protein-1 directly interacts with Kif3a, dynamin-1, and Ribeye and colocalizes with clathrin [ 58 , 65 , 66 ]. This association with key vesicular proteins suggests that it plays a vital role in trafficking [ 58 ].…”

Section: Nonsyndromic Congenital Progressive Retinal Disordersmentioning

confidence: 99%

Ribbon Synapses and Retinal Disease: Review

Frederick

Zenisek

2023

IJMS

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Synaptic ribbons are presynaptic protein complexes that are believed to be important for the transmission of sensory information in the visual system. Ribbons are selectively associated with those synapses where graded changes in membrane potential drive continuous neurotransmitter release. Defective synaptic transmission can arise as a result of the mutagenesis of a single ribbon component. Visual diseases that stem from malfunctions in the presynaptic molecular machinery of ribbon synapses in the retina are rare. In this review, we provide an overview of synaptopathies that give rise to retinal malfunction and our present understanding of the mechanisms that underlie their pathogenesis and discuss muscular dystrophies that exhibit ribbon synapse involvement in the pathology.

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Photoreceptor Compartment-Specific TULP1 Interactomes

Cited by 4 publications

References 68 publications

Ciliary Proteins Repurposed by the Synaptic Ribbon: Trafficking Myristoylated Proteins at Rod Photoreceptor Synapses

Ciliary Proteins Repurposed by the Synaptic Ribbon: Trafficking Myristoylated Proteins at Rod Photoreceptor Synapses

A Novel Cre Recombinase Mouse Strain for Cell-Specific Deletion of Floxed Genes in Ribbon Synapse-Forming Retinal Neurons

Ribbon Synapses and Retinal Disease: Review

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