The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65

Mutations in the MYO7A gene cause a deaf-blindness disorder, known as Usher syndrome 1B. In the retina, the majority of MYO7A is in the retinal pigmented epithelium (RPE), where many of the reactions of the visual retinoid cycle take place. We have observed that the retinas of Myo7a-mutant mice ar...

Full description

Bibliographic Details
Main Authors:	Lopes, Vanda S., Gibbs, Daniel, Libby, Richard T., Aleman, Tomas S., Welch, Darcy L., Lillo, Concepción, Jacobson, Samuel G., Radu, Roxana A., Steel, Karen P., Williams, David S.
Format:	Online
Language:	English
Published:	Oxford University Press 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110002/

id	pubmed-3110002
recordtype	oai_dc
spelling	pubmed-31100022011-06-07 The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65 Lopes, Vanda S. Gibbs, Daniel Libby, Richard T. Aleman, Tomas S. Welch, Darcy L. Lillo, Concepción Jacobson, Samuel G. Radu, Roxana A. Steel, Karen P. Williams, David S. Articles Mutations in the MYO7A gene cause a deaf-blindness disorder, known as Usher syndrome 1B. In the retina, the majority of MYO7A is in the retinal pigmented epithelium (RPE), where many of the reactions of the visual retinoid cycle take place. We have observed that the retinas of Myo7a-mutant mice are resistant to acute light damage. In exploring the basis of this resistance, we found that Myo7a-mutant mice have lower levels of RPE65, the RPE isomerase that has a key role in the retinoid cycle. We show for the first time that RPE65 normally undergoes a light-dependent translocation to become more concentrated in the central region of the RPE cells. This translocation requires MYO7A, so that, in Myo7a-mutant mice, RPE65 is partly mislocalized in the light. RPE65 is degraded more quickly in Myo7a-mutant mice, perhaps due to its mislocalization, providing a plausible explanation for its lower levels. Following a 50–60% photobleach, Myo7a-mutant retinas exhibited increased all-trans-retinyl ester levels during the initial stages of dark recovery, consistent with a deficiency in RPE65 activity. Lastly, MYO7A and RPE65 were co-immunoprecipitated from RPE cell lysate by antibodies against either of the proteins, and the two proteins were partly colocalized, suggesting a direct or indirect interaction. Together, the results support a role for MYO7A in the translocation of RPE65, illustrating the involvement of a molecular motor in the spatiotemporal organization of the retinoid cycle in vision. Oxford University Press 2011-07-01 2011-04-14 /pmc/articles/PMC3110002/ /pubmed/21493626 http://dx.doi.org/10.1093/hmg/ddr155 Text en © The Author 2011. Published by Oxford University Press http://creativecommons.org/licenses/by-nc/2.5/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Lopes, Vanda S. Gibbs, Daniel Libby, Richard T. Aleman, Tomas S. Welch, Darcy L. Lillo, Concepción Jacobson, Samuel G. Radu, Roxana A. Steel, Karen P. Williams, David S.
spellingShingle	Lopes, Vanda S. Gibbs, Daniel Libby, Richard T. Aleman, Tomas S. Welch, Darcy L. Lillo, Concepción Jacobson, Samuel G. Radu, Roxana A. Steel, Karen P. Williams, David S. The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65
author_facet	Lopes, Vanda S. Gibbs, Daniel Libby, Richard T. Aleman, Tomas S. Welch, Darcy L. Lillo, Concepción Jacobson, Samuel G. Radu, Roxana A. Steel, Karen P. Williams, David S.
author_sort	Lopes, Vanda S.
title	The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65
title_short	The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65
title_full	The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65
title_fullStr	The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65
title_full_unstemmed	The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65
title_sort	usher 1b protein, myo7a, is required for normal localization and function of the visual retinoid cycle enzyme, rpe65
description	Mutations in the MYO7A gene cause a deaf-blindness disorder, known as Usher syndrome 1B. In the retina, the majority of MYO7A is in the retinal pigmented epithelium (RPE), where many of the reactions of the visual retinoid cycle take place. We have observed that the retinas of Myo7a-mutant mice are resistant to acute light damage. In exploring the basis of this resistance, we found that Myo7a-mutant mice have lower levels of RPE65, the RPE isomerase that has a key role in the retinoid cycle. We show for the first time that RPE65 normally undergoes a light-dependent translocation to become more concentrated in the central region of the RPE cells. This translocation requires MYO7A, so that, in Myo7a-mutant mice, RPE65 is partly mislocalized in the light. RPE65 is degraded more quickly in Myo7a-mutant mice, perhaps due to its mislocalization, providing a plausible explanation for its lower levels. Following a 50–60% photobleach, Myo7a-mutant retinas exhibited increased all-trans-retinyl ester levels during the initial stages of dark recovery, consistent with a deficiency in RPE65 activity. Lastly, MYO7A and RPE65 were co-immunoprecipitated from RPE cell lysate by antibodies against either of the proteins, and the two proteins were partly colocalized, suggesting a direct or indirect interaction. Together, the results support a role for MYO7A in the translocation of RPE65, illustrating the involvement of a molecular motor in the spatiotemporal organization of the retinoid cycle in vision.
publisher	Oxford University Press
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110002/
_version_	1611458077627777024

The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65

Similar Items