Greasing the protein biosynthesis machinery of photoreceptor neurons

Abstract

Daily phagocytosis of outer segments (OS) places extraordinary demands on protein biosynthesis and trafficking in photoreceptor neurons. While the members and roles of the phototransduction pathway in the OS are well characterized, details about protein trafficking are just beginning to emerge. Phosphodiesterase6 (PDE6), the effector enzyme in phototransduction cascade, serves as an example of the steps multimeric proteins must pass through to achieve their functional state in the OS. Genetic model systems have recently provided snapshots of various steps in the pathway, as experimental difficulties such as an inability to maintain ciliated photoreceptor outer segments or express functional PDE6 holoenzyme in vitro necessitate in vivo studies. We will highlight the significant findings, their implications to blinding diseases, as well as discuss the gaps requiring further investigation.

Keywords: :

• prenylation
• phosphodiesterase
• methylesterification
• rod photoreceptors
• cilia

Acknowledgments

We thank our collaborator Drs Stephen Young and Martin Bergo for animal models, reagents and advice. This work was supported by National Institutes of Health grant RO1EY017035 (V.R.), West Virginia Lions, Lions Club International Foundation, and Research to Prevent Blindness (RPB) challenge grant to West Virginia University.