ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
An unconventional secretory pathway mediates the cilia targeting of peripherin/rds.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 85 citations in OpenAlex.
- The tetraspanin disc proteins, peripherin-2 and ROM1, facilitate CNG channel localization to the rod outer segment.Molecular biology of the cell · 2026Article
- Review
- Visualization of photoreceptor outer segment renewal using AAV-delivered Dendra2-tagged rhodopsin.bioRxiv : the preprint server for biology · 2025Article
- Transcriptional downregulation of rhodopsin is associated with desensitization of rods to light-induced damage in a murine model of retinitis pigmentosa.Human molecular genetics · 2025Article
- Investigation of ABCA4 Missense Variants and Potential Small Molecule Rescue in Retinal Organoids.Investigative ophthalmology & visual science · 2025Article
- Inpp5e is crucial for photoreceptor outer segment maintenance.Journal of cell science · 2025Article
- A new mouse model for PRPH2 pattern dystrophy exhibits functional compensation prior and subsequent to retinal degeneration.Human molecular genetics · 2024Article
- Contribution of intraflagellar transport to compartmentalization and maintenance of the photoreceptor cell.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Coordination of RAB-8 and RAB-11 during unconventional protein secretion.The Journal of cell biology · 2024Article
- Super-resolution mapping in rod photoreceptors identifies rhodopsin trafficking through the inner segment plasma membrane as an essential subcellular pathway.PLoS biology · 2024Article
- The role of syntaxins in retinal function and health.Frontiers in cellular neuroscience · 2024Review
- ROM1 is redundant to PRPH2 as a molecular building block of photoreceptor disc rims.bioRxiv : the preprint server for biology · 2023Article
- Recent advances in the understanding of cilia mechanisms and their applications as therapeutic targets.Frontiers in molecular biosciences · 2023Review
- Cryo-EM structures of peripherin-2 and ROM1 suggest multiple roles in photoreceptor membrane morphogenesis.Science advances · 2022Article
- SMGL-1/NBAS acts as a RAB-8 GEF to regulate unconventional protein secretion.The Journal of cell biology · 2022Article
- Tmem138 is localized to the connecting cilium essential for rhodopsin localization and outer segment biogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Autophagy-Related Pathways in Vesicular Unconventional Protein Secretion.Frontiers in cell and developmental biology · 2022Review
- Comparison of Ciliary Targeting of Two Rhodopsin-Like GPCRs: Role of C-Terminal Localization Sequences in Relation to Cilium Type.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Functional compartmentalization of photoreceptor neurons.Pflugers Archiv : European journal of physiology · 2021Review
- Structure and dynamics of photoreceptor sensory cilia.Pflugers Archiv : European journal of physiology · 2021Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
It is unclear how unconventional secretion interplays with conventional secretion for the normal maintenance and renewal of membrane structures. The photoreceptor sensory cilium is recognized for fast membrane renewal, for which rhodopsin and peripherin/rds (P/rds) play critical roles. Here, we provide evidence that P/rds is targeted to the cilia by an unconventional secretion pathway. When expressed in ciliated hTERT-RPE1 human cell line, P/rd is localized to cilia. Cilium trafficking of P/rds was sustained even when the Golgi functions, including trans-Golgi-mediated conventional secretion, were inhibited by the small molecules brefeldin A, 30N12, and monensin. The unconventional cilia targeting of P/rds is dependent on COPII-mediated exit from the ER, but appears to be independent of GRASP55-mediated secretion. The regions in the C-terminal tail of P/rds are essential for this unconventional trafficking. In the absence of the region required for cilia targeting, P/rds was prohibited from entering the secretory pathways and was retained in the Golgi apparatus. A region essential for this Golgi retention was also found in the C-terminal tail of P/rds and supported the cilia targeting of P/rds mediated by unconventional secretion. In ciliated cells, including bovine and Xenopus laevis rod photoreceptors, P/rds was robustly sensitive to endoglycosidase H, which is consistent with its bypassing the medial Golgi and traversing the unconventional secretory pathway. Because rhodopsin is known to traffic through conventional secretion, this study of P/rds suggests that both conventional secretion and unconventional secretion need to cooperate for the renewal of the photoreceptor sensory cilium.
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