Compartmentalization of Photoreceptor Sensory Cilia

Barnes, Cassandra; Malhotra, Himanshu; Calvert, Peter D.

doi:10.3389/fcell.2021.636737

Cited by 32 publications

(20 citation statements)

References 307 publications

(319 reference statements)

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“…DEGs involved in ciliary transport including tulp1b and arl13a are also increased in P23H. Mutations in tulp1 are reported to contribute to ~5% of total RP cases [32, 33] and mutations in arl13 lead to failure of rod outer segment formation [34, 35]. Interestingly we noted a significant increase in the transcript level of rod arrestins ( saga , sagb ) in P23H compared to the WT (Fig.…”

Section: Resultsmentioning

confidence: 58%

Transcriptomic remodeling of the retina in a Zebrafish model of Retinitis Pigmentosa

Santhanam

Shihabeddin

Wei

et al. 2022

Preprint

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Inherited retinal degenerative diseases such as Retinitis Pigmentosa (RP) result in progressive loss of photoreceptors until an individual is completely blind. A hallmark of these diseases is progressive structural and functional remodeling of the remaining retinal neurons as rod photoreceptors are lost. While many studies focus on regenerative or bionic therapies to restore vision, extensive remodeling of retinal cell types throughout the course of retinal degenerative diseases stands as a barrier for successful implementation of these strategies. As a window onto the molecular basis of remodeling, we have performed a comparative analysis of single-cell transcriptome data from adult Zebrafish retina of wild-type and a P23H mutant rhodopsin model of RP. In addition to providing a benchmark atlas of retinal cell type transcriptomes in the wild-type adult Zebrafish retina, we find transcriptional changes in essentially all retinal cell types in the P23H model. Increased oxidative stress is evident not only in the rods but also in cones, retinal pigmented epithelium (RPE) and to a lesser extent in amacrine and bipolar cells. Metabolic changes increasing oxidative metabolism and glycolysis are found in rods and cones, while evidence of increased activity of the mitochondrial electron transport chain is found in retinal ganglion cells (RGCs). Evidence of synaptic remodeling is found throughout the retina, with changes to increase synaptic transmission in photoreceptors and bipolar cells, increased ionotropic glutamate receptors in amacrine and ganglion cells, and dendritic and axon remodeling throughout. Surprisingly, RPE, cones and bipolar cells in the P23H retinas also have increased expression of genes involved in circadian rhythm regulation. While this model system undergoes continuous regeneration, ongoing remodeling impacts the entire retina. This comprehensive transcriptomic analysis provides a molecular road map to understand how the retina remodels in the context of chronic retinal degeneration with ongoing regeneration.

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Section: Resultsmentioning

confidence: 58%

Transcriptomic remodeling of the retina in a Zebrafish model of Retinitis Pigmentosa

Santhanam

Shihabeddin

Wei

et al. 2022

Preprint

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show abstract

“…This pathway may not be absolutely essential for all protein transport but may instead regulate their ciliary levels, as previously proposed [50]. Evidence from numerous studies suggest that the mechanisms underlying protein trafficking in and out of cilia are complex and likely involves multiple processes, including diffusion, localization signals, and IFT motor-driven pathways [56,57].…”

Section: Discussionmentioning

confidence: 93%

Photoreceptor Compartment-Specific TULP1 Interactomes

Ebke

Sinha

Pauer

et al. 2021

Preprint

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Photoreceptors are highly compartmentalized cells with large amounts of proteins synthesized in the inner segment (IS) and transported to the outer segment (OS) and synaptic terminal. Tulp1 is a photoreceptor-specific protein localized to the IS and synapse. In the absence of Tulp1, sev-eral OS-specific proteins are mislocalized and synaptic vesicle recycling is impaired. To better understand the involvement of Tulp1 in protein trafficking, our approach was to physically iso-late Tulp1-containing photoreceptor compartments by serial tangential sectioning of retinas and to identify compartment-specific Tulp1 binding partners by immunoprecipitation followed by liquid chromatography tandem mass spectrometry. Our results indicate that Tulp1 has two dis-tinct interactomes. We report the identification of: 1) an IS-specific interaction between Tulp1 and the motor protein Kinesin family member 3a (Kif3a), 2) a synaptic-specific interaction be-tween Tulp1 and the scaffold protein Ribeye, and 3) an interaction between Tulp1 and the cyto-skeletal protein Microtubule-associated protein 1B (MAP1B) in both compartments. Immuno-localization studies in the wild-type retina indicate that Tulp1 and its binding partners co-localize to their respective compartments. Our observations are compatible with Tulp1 functioning in protein trafficking in multiple photoreceptor compartments, likely as an adapter molecule linking vesicles to molecular motors and the cytoskeletal scaffold.

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“…This pathway may not be absolutely essential for all protein transport but may instead regulate their ciliary levels, as previously proposed [ 50 ]. Evidence from numerous studies suggests that the mechanisms underlying protein trafficking in and out of cilia are complex and likely involve multiple processes, including diffusion, localization signals, and IFT motor-driven pathways [ 56 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

Photoreceptor Compartment-Specific TULP1 Interactomes

Ebke

Sinha

Pauer

et al. 2021

IJMS

View full text Add to dashboard Cite

Photoreceptors are highly compartmentalized cells with large amounts of proteins synthesized in the inner segment (IS) and transported to the outer segment (OS) and synaptic terminal. Tulp1 is a photoreceptor-specific protein localized to the IS and synapse. In the absence of Tulp1, several OS-specific proteins are mislocalized and synaptic vesicle recycling is impaired. To better understand the involvement of Tulp1 in protein trafficking, our approach in the current study was to physically isolate Tulp1-containing photoreceptor compartments by serial tangential sectioning of retinas and to identify compartment-specific Tulp1 binding partners by immunoprecipitation followed by liquid chromatography tandem mass spectrometry. Our results indicate that Tulp1 has two distinct interactomes. We report the identification of: (1) an IS-specific interaction between Tulp1 and the motor protein Kinesin family member 3a (Kif3a), (2) a synaptic-specific interaction between Tulp1 and the scaffold protein Ribeye, and (3) an interaction between Tulp1 and the cytoskeletal protein microtubule-associated protein 1B (MAP1B) in both compartments. Immunolocalization studies in the wild-type retina indicate that Tulp1 and its binding partners co-localize to their respective compartments. Our observations are compatible with Tulp1 functioning in protein trafficking in multiple photoreceptor compartments, likely as an adapter molecule linking vesicles to molecular motors and the cytoskeletal scaffold.

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Compartmentalization of Photoreceptor Sensory Cilia

Cited by 32 publications

References 307 publications

Transcriptomic remodeling of the retina in a Zebrafish model of Retinitis Pigmentosa

Transcriptomic remodeling of the retina in a Zebrafish model of Retinitis Pigmentosa

Photoreceptor Compartment-Specific TULP1 Interactomes

Photoreceptor Compartment-Specific TULP1 Interactomes

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