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ARL2BP, a protein linked to retinitis pigmentosa, is needed for normal photoreceptor cilia doublets and outer segment structure

The outer segment (OS) of photoreceptor cells is an elaboration of a primary cilium with organized stacks of membranous disks that contain the proteins needed for phototransduction and vision. Though ciliary formation and function has been well characterized, little is known about the role of cilia...

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Autores principales: Moye, Abigail R., Singh, Ratnesh, Kimler, Victoria A., Dilan, Tanya L., Munezero, Daniella, Saravanan, Thamaraiselvi, Goldberg, Andrew F. X., Ramamurthy, Visvanathan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080659/
https://www.ncbi.nlm.nih.gov/pubmed/29718757
http://dx.doi.org/10.1091/mbc.E18-01-0040
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author Moye, Abigail R.
Singh, Ratnesh
Kimler, Victoria A.
Dilan, Tanya L.
Munezero, Daniella
Saravanan, Thamaraiselvi
Goldberg, Andrew F. X.
Ramamurthy, Visvanathan
author_facet Moye, Abigail R.
Singh, Ratnesh
Kimler, Victoria A.
Dilan, Tanya L.
Munezero, Daniella
Saravanan, Thamaraiselvi
Goldberg, Andrew F. X.
Ramamurthy, Visvanathan
author_sort Moye, Abigail R.
collection PubMed
description The outer segment (OS) of photoreceptor cells is an elaboration of a primary cilium with organized stacks of membranous disks that contain the proteins needed for phototransduction and vision. Though ciliary formation and function has been well characterized, little is known about the role of cilia in the development of photoreceptor OS. Nevertheless, progress has been made by studying mutations in ciliary proteins, which often result in malformed OSs and lead to blinding diseases. To investigate how ciliary proteins contribute to OS formation, we generated a knockout (KO) mouse model for ARL2BP, a ciliary protein linked to retinitis pigmentosa. The KO mice display an early and progressive reduction in visual response. Before photoreceptor degeneration, we observed disorganization of the photoreceptor OS, with vertically aligned disks and shortened axonemes. Interestingly, ciliary doublet microtubule (MT) structure was also impaired, displaying open B-tubule doublets, paired with loss of singlet MTs. On the basis of results from this study, we conclude that ARL2BP is necessary for photoreceptor ciliary doublet formation and axoneme elongation, which is required for OS morphogenesis and vision.
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spelling pubmed-60806592018-09-16 ARL2BP, a protein linked to retinitis pigmentosa, is needed for normal photoreceptor cilia doublets and outer segment structure Moye, Abigail R. Singh, Ratnesh Kimler, Victoria A. Dilan, Tanya L. Munezero, Daniella Saravanan, Thamaraiselvi Goldberg, Andrew F. X. Ramamurthy, Visvanathan Mol Biol Cell Articles The outer segment (OS) of photoreceptor cells is an elaboration of a primary cilium with organized stacks of membranous disks that contain the proteins needed for phototransduction and vision. Though ciliary formation and function has been well characterized, little is known about the role of cilia in the development of photoreceptor OS. Nevertheless, progress has been made by studying mutations in ciliary proteins, which often result in malformed OSs and lead to blinding diseases. To investigate how ciliary proteins contribute to OS formation, we generated a knockout (KO) mouse model for ARL2BP, a ciliary protein linked to retinitis pigmentosa. The KO mice display an early and progressive reduction in visual response. Before photoreceptor degeneration, we observed disorganization of the photoreceptor OS, with vertically aligned disks and shortened axonemes. Interestingly, ciliary doublet microtubule (MT) structure was also impaired, displaying open B-tubule doublets, paired with loss of singlet MTs. On the basis of results from this study, we conclude that ARL2BP is necessary for photoreceptor ciliary doublet formation and axoneme elongation, which is required for OS morphogenesis and vision. The American Society for Cell Biology 2018-07-01 /pmc/articles/PMC6080659/ /pubmed/29718757 http://dx.doi.org/10.1091/mbc.E18-01-0040 Text en © 2018 Moye et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Articles
Moye, Abigail R.
Singh, Ratnesh
Kimler, Victoria A.
Dilan, Tanya L.
Munezero, Daniella
Saravanan, Thamaraiselvi
Goldberg, Andrew F. X.
Ramamurthy, Visvanathan
ARL2BP, a protein linked to retinitis pigmentosa, is needed for normal photoreceptor cilia doublets and outer segment structure
title ARL2BP, a protein linked to retinitis pigmentosa, is needed for normal photoreceptor cilia doublets and outer segment structure
title_full ARL2BP, a protein linked to retinitis pigmentosa, is needed for normal photoreceptor cilia doublets and outer segment structure
title_fullStr ARL2BP, a protein linked to retinitis pigmentosa, is needed for normal photoreceptor cilia doublets and outer segment structure
title_full_unstemmed ARL2BP, a protein linked to retinitis pigmentosa, is needed for normal photoreceptor cilia doublets and outer segment structure
title_short ARL2BP, a protein linked to retinitis pigmentosa, is needed for normal photoreceptor cilia doublets and outer segment structure
title_sort arl2bp, a protein linked to retinitis pigmentosa, is needed for normal photoreceptor cilia doublets and outer segment structure
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080659/
https://www.ncbi.nlm.nih.gov/pubmed/29718757
http://dx.doi.org/10.1091/mbc.E18-01-0040
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