Researchers discover molecular light switch in photoreceptor cells

Researchers discover molecular light switch in photoreceptor cells
Fig.1. Light and dark adaptation. In low light, dark adaptation is achieved by increasing photosensitivity. Under bright conditions, light adaptation is achieved by decreasing photosensitivity. Credit: Osaka University

How our eyes detect and respond to changes in light intensity is determined by specialized cells in the eye called photoreceptors. In addition to converting light into electrical signals, effectively allowing us to see, rod-shaped photoreceptors adapt to changes in light intensity to protect the eye from damage caused by excessive light exposure. However, in conditions such as retinitis pigmentosa, these cells do not work properly, leading to progressive vision loss. Now, researchers from Japan's Osaka University have identified the protein responsible for the "switch" between light and dark adaptation.

In the study published this month in The EMBO Journal, the researchers describe how the of the newly identified protein, Cul3-Klhl18 ubiquitin ligase, helps control the response of rod photoreceptors to changes in .

Rod contain a protein called transducin, which is part of the phototransduction cascade. "Under dark-adapted conditions, transducin is concentrated near the outer part of the cells," explains lead author of the study Taro Chaya. "When light is detected, the transducin proteins move down into the inner section of the rod photoreceptor cells, modulating photosensitivity. However, previously no one has determined how this process is regulated."

To identify genes involved in regulating photosensitivity, the researchers compared in healthy mice and those with defective photoreceptor cells. One gene, Klhl18, stood out because it was predominantly expressed in the retina, specifically in the outer layer where photoreceptor cells are located. More importantly, the in vivo function of the gene product, Cul3-Klhl18 ubiquitin ligase, had been unclear.

Researchers discover molecular light switch in photoreceptor cells
Fig. 2. Summary of results. Credit: Osaka University

To confirm the importance of Klhl18, the researchers generated a Klhl18-deficient mouse line and examined how the mice responded to changes in light intensity. Sure enough, the mice missing Cul3-Klhl18 ubiquitin ligase showed reduced responsiveness to light, and transducin remained in the inner section of rod photoreceptor cells. Importantly though, the Klhl18-deficient mice were less susceptible to light-induced photoreceptor damage compared with their normal counterparts.

Researchers discover molecular light switch in photoreceptor cells
Fig.3. Klhl18 deficiency suppresses light-induced retinal damage. Credit: Osaka University

"We then wanted to know how Cul3-Klhl18 ubiquitin ligase interacts with transducin in the cells," says senior author Takahisa Furukawa. "Transducin is moved around the cell by a protein called Unc119. When we studied the system more closely, we found that in the dark, Unc119 is tagged with something called ubiquitin and then degraded by the Cul3-Klhl18 ligase, allowing translocation of transducing to the outer part of photoreceptor cells. Upon light exposure, Unc119 is phosphorylated, preventing degradation and transducin migration." These results suggest that therapies aimed at inhibiting Cul3-Klhl18 ubiquitin ligase may help treat degenerative retinal diseases such as and retinitis pigmentosa.

The article, "Cul3-Klhl18 ubiquitin ligase modulates rod transducin translocation during light-dark adaptation," was published in The EMBO Journal.


Explore further

MIB2 enhances inflammation by degradation of CYLD

More information: Taro Chaya et al. Cul3‐Klhl18 ubiquitin ligase modulates rod transducin translocation during light‐dark adaptation, The EMBO Journal (2019). DOI: 10.15252/embj.2018101409
Journal information: EMBO Journal

Provided by Osaka University
Citation: Researchers discover molecular light switch in photoreceptor cells (2019, November 20) retrieved 11 December 2019 from https://phys.org/news/2019-11-molecular-photoreceptor-cells.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
140 shares

Feedback to editors

User comments