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

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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.

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

Keywords

Animals
Drosophila Proteins
Drosophila melanogaster
Endocytosis
Light
Lysosomes
Mutation
Photoreceptor Cells, Invertebrate
Protein Transport
Retinal Degeneration
Rhodopsin
Vesicular Transport Proteins
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

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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), 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, W-L, 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, pp. 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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author = "Shiuan Wang and Tan, {Kai Li} and Agosto, {Melina A} and Bo Xiong and Shinya Yamamoto and Hector Sandoval and Manish Jaiswal and Vafa Bayat and Ke Zhang and Wu-Lin Charng and Gabriela David and Lita Duraine and Kartik Venkatachalam and Wensel, {Theodore G} and Bellen, {Hugo J}",

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AU - Wang, Shiuan

AU - Tan, Kai Li

AU - Agosto, Melina A

AU - Xiong, Bo

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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AB - 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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KW - Drosophila Proteins

KW - Drosophila melanogaster

KW - Endocytosis

KW - Light

KW - Lysosomes

KW - Mutation

KW - Photoreceptor Cells, Invertebrate

KW - Protein Transport

KW - Retinal Degeneration

KW - Rhodopsin

KW - Vesicular Transport Proteins

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

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DO - 10.1371/journal.pbio.1001847

M3 - Article

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SN - 1545-7885

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SP - e1001847

JO - PLoS biology

JF - PLoS biology

IS - 4

ER -

The retromer complex is required for rhodopsin recycling and its loss leads to photoreceptor degeneration

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Keywords

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