Vision is initiated in the retina where light is captured in the outer segment organelle of photoreceptor cells. The outer segment is unique in that it is a modified primary cilium that contains large quantities of proteins involved in visual signal transduction. Notably, the outer segment lacks the machinery used to synthesize proteins and therefore relies on the import of proteins synthesized in the cell's soma. Very little is known about the intracellular trafficking of proteins from their site of synthesis to the outer segment. Only the trafficking pathway for the visual pigment, rhodopsin, has been described and it is currently unknown whether other proteins use the same or different pathways. Thus the first aim of my proposal is to determine how another outer segment protein, peripherin, is delivered to the outer segment. Peripherin was selected because its outer segment targeting relies on a motif distinct from that of rhodopsin, suggesting that it may utilize a distinct transport mechanism.
My second aim i s to explore the universality of protein targeting motifs between photoreceptors and other types of ciliary cells. I will examine whether different types of cilia us the same targeting information and molecular machinery to deliver proteins. This project has broad implications for understanding cellular mechanisms responsible for specific protein delivery to the outer segment and other cilia, as well as elucidating how mutations of the trafficking machinery can lead to retinal degeneration in photoreceptors and ciliary dysfunction in other cell types.

Public Health Relevance

Humans suffering from blindness and severe visual impairments often have genetic mutations that affect the proper transport of proteins within the photoreceptor cell. This proposal addresses the mechanisms responsible for targeted protein trafficking to the light sensing compartment of the photoreceptor. This will further our understanding of inherited retinal diseases and provide scientific background for developing future therapeutic approaches to treat these devastating diseases.

Agency
National Institute of Health (NIH)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31EY022862-03
Application #
8678932
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Agarwal, Neeraj
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Duke University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
City
Durham
State
NC
Country
United States
Zip Code
27705
Pearring, Jillian N; Salinas, Raquel Y; Baker, Sheila A et al. (2013) Protein sorting, targeting and trafficking in photoreceptor cells. Prog Retin Eye Res 36:24-51