The Retromer Complex Is Required for Rhodopsin Recycling and Its Loss Leads to Photoreceptor Degeneration

Shiuan Wang; Kai Li Tan; Melina A. Agosto; Bo Xiong; Shinya Yamamoto; Hector Sandoval; Manish Jaiswal; Vafa Bayat; Ke Zhang; Wu Lin Charng; Gabriela David; Lita Duraine; Kartik Venkatachalam; Theodore G. Wensel; Hugo J. Bellen

doi:10.1371/journal.pbio.1001847

The Retromer Complex Is Required for Rhodopsin Recycling and Its Loss Leads to Photoreceptor Degeneration

Shiuan Wang, Kai Li Tan, Melina A. Agosto, Bo Xiong, Shinya Yamamoto, Hector Sandoval, Manish Jaiswal, Vafa Bayat, Ke Zhang, Wu Lin Charng, Gabriela David, Lita Duraine, Kartik Venkatachalam, Theodore G. Wensel, Hugo J. Bellen

Molecular Neuroscience

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

Abstract

Rhodopsin mistrafficking can cause photoreceptor (PR) degeneration. Upon light exposure, activated rhodopsin 1 (Rh1) in Drosophila PRs is internalized via endocytosis and degraded in lysosomes. Whether internalized Rh1 can be recycled is unknown. Here, we show that the retromer complex is expressed in PRs where it is required for recycling endocytosed Rh1 upon light stimulation. In the absence of subunits of the retromer, Rh1 is processed in the endolysosomal pathway, leading to a dramatic increase in late endosomes, lysosomes, and light-dependent PR degeneration. Reducing Rh1 endocytosis or Rh1 levels in retromer mutants alleviates PR degeneration. In addition, increasing retromer abundance suppresses degenerative phenotypes of mutations that affect the endolysosomal system. Finally, expressing human Vps26 suppresses PR degeneration in Vps26 mutant PRs. We propose that the retromer plays a conserved role in recycling rhodopsins to maintain PR function and integrity.

Original language	English (US)
Article number	e1001847
Journal	PLoS biology
Volume	12
Issue number	4
DOIs	https://doi.org/10.1371/journal.pbio.1001847
State	Published - 2014

ASJC Scopus subject areas

General Neuroscience
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology
General Agricultural and Biological Sciences

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10.1371/journal.pbio.1001847

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Wang, S., Tan, K. L., Agosto, M. A., Xiong, B., Yamamoto, S., Sandoval, H., Jaiswal, M., Bayat, V., Zhang, K., Charng, W. L., David, G., Duraine, L., Venkatachalam, K., Wensel, T. G., & Bellen, H. J. (2014). The Retromer Complex Is Required for Rhodopsin Recycling and Its Loss Leads to Photoreceptor Degeneration. PLoS biology, 12(4), Article e1001847. https://doi.org/10.1371/journal.pbio.1001847

Wang, S, Tan, KL, Agosto, MA, Xiong, B, Yamamoto, S, Sandoval, H, Jaiswal, M, Bayat, V, Zhang, K, Charng, WL, David, G, Duraine, L, Venkatachalam, K, Wensel, TG & Bellen, HJ 2014, 'The Retromer Complex Is Required for Rhodopsin Recycling and Its Loss Leads to Photoreceptor Degeneration', PLoS biology, vol. 12, no. 4, e1001847. https://doi.org/10.1371/journal.pbio.1001847

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abstract = "Rhodopsin mistrafficking can cause photoreceptor (PR) degeneration. Upon light exposure, activated rhodopsin 1 (Rh1) in Drosophila PRs is internalized via endocytosis and degraded in lysosomes. Whether internalized Rh1 can be recycled is unknown. Here, we show that the retromer complex is expressed in PRs where it is required for recycling endocytosed Rh1 upon light stimulation. In the absence of subunits of the retromer, Rh1 is processed in the endolysosomal pathway, leading to a dramatic increase in late endosomes, lysosomes, and light-dependent PR degeneration. Reducing Rh1 endocytosis or Rh1 levels in retromer mutants alleviates PR degeneration. In addition, increasing retromer abundance suppresses degenerative phenotypes of mutations that affect the endolysosomal system. Finally, expressing human Vps26 suppresses PR degeneration in Vps26 mutant PRs. We propose that the retromer plays a conserved role in recycling rhodopsins to maintain PR function and integrity.",

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AU - Yamamoto, Shinya

AU - Sandoval, Hector

AU - Jaiswal, Manish

AU - Bayat, Vafa

AU - Zhang, Ke

AU - Charng, Wu Lin

AU - David, Gabriela

AU - Duraine, Lita

AU - Venkatachalam, Kartik

AU - Wensel, Theodore G.

AU - Bellen, Hugo J.

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The Retromer Complex Is Required for Rhodopsin Recycling and Its Loss Leads to Photoreceptor Degeneration

Abstract

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