ROM1 is redundant to PRPH2 as a molecular building block of photoreceptor disc rims
Visual signal transduction takes place within a stack of flattened membranous ‘discs’ enclosed within the light-sensitive photoreceptor outer segment. The highly curved rims of these discs, formed in the process of disc enclosure, are fortified by large hetero-oligomeric complexes of two homologous...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2023-11-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/89444 |
| _version_ | 1797517103342813184 |
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| author | Tylor R Lewis Mustafa S Makia Carson M Castillo Ying Hao Muayyad R Al-Ubaidi Nikolai P Skiba Shannon M Conley Vadim Y Arshavsky Muna I Naash |
| author_facet | Tylor R Lewis Mustafa S Makia Carson M Castillo Ying Hao Muayyad R Al-Ubaidi Nikolai P Skiba Shannon M Conley Vadim Y Arshavsky Muna I Naash |
| author_sort | Tylor R Lewis |
| collection | DOAJ |
| description | Visual signal transduction takes place within a stack of flattened membranous ‘discs’ enclosed within the light-sensitive photoreceptor outer segment. The highly curved rims of these discs, formed in the process of disc enclosure, are fortified by large hetero-oligomeric complexes of two homologous tetraspanin proteins, PRPH2 (a.k.a. peripherin-2 or rds) and ROM1. While mutations in PRPH2 affect the formation of disc rims, the role of ROM1 remains poorly understood. In this study, we found that the knockout of ROM1 causes a compensatory increase in the disc content of PRPH2. Despite this increase, discs of ROM1 knockout mice displayed a delay in disc enclosure associated with a large diameter and lack of incisures in mature discs. Strikingly, further increasing the level of PRPH2 rescued these morphological defects. We next showed that disc rims are still formed in a knockin mouse in which the tetraspanin body of PRPH2 was replaced with that of ROM1. Together, these results demonstrate that, despite its contribution to the formation of disc rims, ROM1 can be replaced by an excess of PRPH2 for timely enclosure of newly forming discs and establishing normal outer segment structure. |
| first_indexed | 2024-03-10T07:10:09Z |
| format | Article |
| id | doaj.art-f1a6b2b27aea469492cc14481ac299ac |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-10T07:10:09Z |
| publishDate | 2023-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f1a6b2b27aea469492cc14481ac299ac2023-11-22T15:30:27ZengeLife Sciences Publications LtdeLife2050-084X2023-11-011210.7554/eLife.89444ROM1 is redundant to PRPH2 as a molecular building block of photoreceptor disc rimsTylor R Lewis0https://orcid.org/0000-0001-6832-7972Mustafa S Makia1Carson M Castillo2Ying Hao3Muayyad R Al-Ubaidi4Nikolai P Skiba5Shannon M Conley6Vadim Y Arshavsky7https://orcid.org/0000-0001-8394-3650Muna I Naash8Department of Ophthalmology, Duke University Medical Center, Durham, United StatesDepartment of Biomedical Engineering, University of Houston, Houston, United StatesDepartment of Ophthalmology, Duke University Medical Center, Durham, United StatesDepartment of Ophthalmology, Duke University Medical Center, Durham, United StatesDepartment of Biomedical Engineering, University of Houston, Houston, United States; College of Optometry, University of Houston, Houston, United StatesDepartment of Ophthalmology, Duke University Medical Center, Durham, United StatesDepartment of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, United StatesDepartment of Ophthalmology, Duke University Medical Center, Durham, United States; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, United StatesDepartment of Biomedical Engineering, University of Houston, Houston, United States; College of Optometry, University of Houston, Houston, United StatesVisual signal transduction takes place within a stack of flattened membranous ‘discs’ enclosed within the light-sensitive photoreceptor outer segment. The highly curved rims of these discs, formed in the process of disc enclosure, are fortified by large hetero-oligomeric complexes of two homologous tetraspanin proteins, PRPH2 (a.k.a. peripherin-2 or rds) and ROM1. While mutations in PRPH2 affect the formation of disc rims, the role of ROM1 remains poorly understood. In this study, we found that the knockout of ROM1 causes a compensatory increase in the disc content of PRPH2. Despite this increase, discs of ROM1 knockout mice displayed a delay in disc enclosure associated with a large diameter and lack of incisures in mature discs. Strikingly, further increasing the level of PRPH2 rescued these morphological defects. We next showed that disc rims are still formed in a knockin mouse in which the tetraspanin body of PRPH2 was replaced with that of ROM1. Together, these results demonstrate that, despite its contribution to the formation of disc rims, ROM1 can be replaced by an excess of PRPH2 for timely enclosure of newly forming discs and establishing normal outer segment structure.https://elifesciences.org/articles/89444visionretinaphotoreceptorouter segmentciliatetraspanin |
| spellingShingle | Tylor R Lewis Mustafa S Makia Carson M Castillo Ying Hao Muayyad R Al-Ubaidi Nikolai P Skiba Shannon M Conley Vadim Y Arshavsky Muna I Naash ROM1 is redundant to PRPH2 as a molecular building block of photoreceptor disc rims eLife vision retina photoreceptor outer segment cilia tetraspanin |
| title | ROM1 is redundant to PRPH2 as a molecular building block of photoreceptor disc rims |
| title_full | ROM1 is redundant to PRPH2 as a molecular building block of photoreceptor disc rims |
| title_fullStr | ROM1 is redundant to PRPH2 as a molecular building block of photoreceptor disc rims |
| title_full_unstemmed | ROM1 is redundant to PRPH2 as a molecular building block of photoreceptor disc rims |
| title_short | ROM1 is redundant to PRPH2 as a molecular building block of photoreceptor disc rims |
| title_sort | rom1 is redundant to prph2 as a molecular building block of photoreceptor disc rims |
| topic | vision retina photoreceptor outer segment cilia tetraspanin |
| url | https://elifesciences.org/articles/89444 |
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