ArticleProceedings of the National Academy of Sciences of the United States of America2022
Tmem138 is localized to the connecting cilium essential for rhodopsin localization and outer segment biogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 21 citations in OpenAlex.
- Ciliary Defects in Inherited Retinal Diseases.Advanced genetics (Hoboken, N.J.) · 2026Review
- Rod-Cone Dystrophy Related WDR34 Is Essential for Ciliary Integrity and Survival of Mammalian Photoreceptor Cells.Investigative ophthalmology & visual science · 2026Article
- Visualization of photoreceptor outer segment renewal using AAV-delivered Dendra2-tagged rhodopsin.bioRxiv : the preprint server for biology · 2025Article
- Foxn3 is required to suppress aberrant ciliogenesis in nonphotoreceptor retinal neurons.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- P23H rhodopsin accumulation causes transient disruptions to synaptic protein levels in rod photoreceptors in a model of retinitis pigmentosa.Disease models & mechanisms · 2025Article
- TMEM138: From Biological Functions to Diseases.Physiological research · 2025Review
- Ciliopathy-associated protein, CEP290, is required for ciliary necklace and outer segment membrane formation in retinal photoreceptors.bioRxiv : the preprint server for biology · 2025Article
- Progressive Optic Neuropathy in Hydrocephalic Ccdc13 Mutant Mice Caused by Impaired Axoplasmic Transport at the Optic Nerve Head.Investigative ophthalmology & visual science · 2024Article
- Prickle1-driven basement membrane deposition of the iPSC-derived embryoid bodies is separable from the establishment of apicobasal polarity.Cell proliferation · 2024Article
- Super-resolution mapping in rod photoreceptors identifies rhodopsin trafficking through the inner segment plasma membrane as an essential subcellular pathway.PLoS biology · 2024Article
- Dysregulated Arginine Metabolism Is Linked to Retinal Degeneration in Cep250 Knockout Mice.Investigative ophthalmology & visual science · 2023Article
- Single-Cell Characterization of the Frizzled 5 (Fz5) Mutant Mouse and Human Persistent Fetal Vasculature (PFV).Investigative ophthalmology & visual science · 2023Article
- Bardet-Biedl Syndrome: Current Perspectives and Clinical Outlook.Therapeutics and clinical risk management · 2023Review
- Extracellular vesicles highlight many cases of photoreceptor degeneration.Frontiers in molecular neuroscience · 2023Review
- Molecular characteristics and transcriptional regulatory of spermatogenesis-related geneAnimal reproduction · 2023Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Photoreceptor connecting cilium (CC) is structurally analogous to the transition zone (TZ) of primary cilia and gates the molecular trafficking between the inner and the outer segment (OS). Retinal dystrophies with underlying CC defects are manifested in a broad array of syndromic conditions known as ciliopathies as well as nonsyndromic retinal degenerations. Despite extensive studies, many questions remain in the mechanism of protein trafficking across the photoreceptor CC. Here, we genetically inactivated mouse Tmem138, a gene encoding a putative transmembrane protein localized to the ciliary TZ and linked to ciliopathies. Germline deletion of Tmem138 abolished OS morphogenesis, followed by rapid photoreceptor degeneration. Tmem138 was found localized to the photoreceptor CC and was required for localization of Ahi1 to the distal subdomain of the CC. Among the examined set of OS proteins, rhodopsin was mislocalized throughout the mutant cell body prior to OS morphogenesis. Ablation of Tmem138 in mature rods recapitulated the molecular changes in the germline mutants, causing failure of disc renewal and disintegration of the OS. Furthermore, Tmem138 interacts reciprocally with rhodopsin and a related protein Tmem231, and the ciliary localization of the latter was also altered in the mutant photoreceptors. Taken together, these results suggest a crucial role of Tmem138 in the functional organization of the CC, which is essential for rhodopsin localization and OS biogenesis.
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