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Contribution of intraflagellar transport to compartmentalization and maintenance of the photoreceptor cell.

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Title: Contribution of intraflagellar transport to compartmentalization and maintenance of the photoreceptor cell.
Authors: Lewisa, Tylor R.1,2 tylor.lewis@duke.edu, Castillo, Carson M.1, Klementieva, Natalia V.1, Ying Hsu2, Ying Hao1, Spencer, William J.3, Drack, Arlene V.2, Pazour, Gregory J.3, Arshavsky, Vadim Y.1,4 vadim.arshavsky@duke.edu
Source: Proceedings of the National Academy of Sciences of the United States of America. 8/20/2024, Vol. 121 Issue 34, p1-12. 27p.
Subjects: Carrier proteins, Diffusion barriers, Rhodopsin, Retinal diseases, Extracellular vesicles
Abstract: The first steps of vision take place in the ciliary outer segment compartment of photoreceptor cells. The protein composition of outer segments is uniquely suited to perform this function. The most abundant among these proteins is the visual pigment, rhodopsin, whose outer segment trafficking involves intraflagellar transport (IFT). Here, we report three major findings from the analysis of mice in which ciliary transport was acutely impaired by conditional knockouts of IFT-B subunits. First, we demonstrate the existence of a sorting mechanism whereby mislocalized rhodopsin is recruited to and concentrated in extracellular vesicles prior to their release, presumably to protect the cell from adverse effects of protein mislocalization. Second, reducing rhodopsin expression significantly delays photoreceptor degeneration caused by IFT disruption, suggesting that controlling rhodopsin levels may be an effective therapy for some cases of retinal degenerative disease. Last, the loss of IFT-B subunits does not recapitulate a phenotype observed in mutants of the BBSome (another ciliary transport protein complex relying on IFT) in which non-ciliary proteins accumulate in the outer segment. Whereas it is widely thought that the role of the BBSome is to primarily participate in ciliary transport, our data suggest that the BBSome has another major function independent of IFT and possibly related to maintaining the diffusion barrier of the ciliary transition zone. [ABSTRACT FROM AUTHOR]
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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DbLabel: Engineering Source
An: 179162741
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PubTypeId: academicJournal
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  Data: Contribution of intraflagellar transport to compartmentalization and maintenance of the photoreceptor cell.
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  Data: <searchLink fieldCode="AR" term="%22Lewisa%2C+Tylor+R%2E%22">Lewisa, Tylor R.</searchLink><relatesTo>1,2</relatesTo><i> tylor.lewis@duke.edu</i><br /><searchLink fieldCode="AR" term="%22Castillo%2C+Carson+M%2E%22">Castillo, Carson M.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Klementieva%2C+Natalia+V%2E%22">Klementieva, Natalia V.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Ying+Hsu%22">Ying Hsu</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Ying+Hao%22">Ying Hao</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Spencer%2C+William+J%2E%22">Spencer, William J.</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Drack%2C+Arlene+V%2E%22">Drack, Arlene V.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Pazour%2C+Gregory+J%2E%22">Pazour, Gregory J.</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Arshavsky%2C+Vadim+Y%2E%22">Arshavsky, Vadim Y.</searchLink><relatesTo>1,4</relatesTo><i> vadim.arshavsky@duke.edu</i>
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  Data: The first steps of vision take place in the ciliary outer segment compartment of photoreceptor cells. The protein composition of outer segments is uniquely suited to perform this function. The most abundant among these proteins is the visual pigment, rhodopsin, whose outer segment trafficking involves intraflagellar transport (IFT). Here, we report three major findings from the analysis of mice in which ciliary transport was acutely impaired by conditional knockouts of IFT-B subunits. First, we demonstrate the existence of a sorting mechanism whereby mislocalized rhodopsin is recruited to and concentrated in extracellular vesicles prior to their release, presumably to protect the cell from adverse effects of protein mislocalization. Second, reducing rhodopsin expression significantly delays photoreceptor degeneration caused by IFT disruption, suggesting that controlling rhodopsin levels may be an effective therapy for some cases of retinal degenerative disease. Last, the loss of IFT-B subunits does not recapitulate a phenotype observed in mutants of the BBSome (another ciliary transport protein complex relying on IFT) in which non-ciliary proteins accumulate in the outer segment. Whereas it is widely thought that the role of the BBSome is to primarily participate in ciliary transport, our data suggest that the BBSome has another major function independent of IFT and possibly related to maintaining the diffusion barrier of the ciliary transition zone. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1073/pnas.2408551121
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        Text: English
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        Type: general
      – SubjectFull: Diffusion barriers
        Type: general
      – SubjectFull: Rhodopsin
        Type: general
      – SubjectFull: Retinal diseases
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      – SubjectFull: Extracellular vesicles
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      – TitleFull: Contribution of intraflagellar transport to compartmentalization and maintenance of the photoreceptor cell.
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              Text: 8/20/2024
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