The goal of this research program is to study the function of a novel photoreceptor specific cadherin (prCAD) that we recently identified. In our preliminary studies we showed that prCAD, a novel member of the cadherin family of cell adhesion proteins, is expressed only in retinal photoreceptors. We used immunoelectron microscopy to localize the prCAD protein to the margins of nascent membrane disks at the base of the photoreceptor outer segments (OS). We produced prCAD (-/-) mice and showed that in these mice the OS are disorganized and fragmented and there is progressive death of photoreceptor cells. The unique localization of prCAD to the base of the OS and the disrupted morphology of the OS in the mutant mice indicate an essential role for prCAD in the biosynthesis or maintenance of the outer segment. The prCAD (-/-) phenotype in the mouse and the high degree of conservation in the prCAD sequences between mice and humans predicts that mutations in human prCAD are likely to cause retinal diseases.
We aim to (1) develop methods for expression of recombinant prCAD in photoreceptors of zebrafish and Xenopus to test the effect of mutations on the structure and function of this protein, (2) identify disease-associated mutations in human prCAD and study their function, (3) identify prCAD interacting proteins and study their role in outer segment morphogenesis, and (4) detect genes and signaling pathways that are differentially regulated in the prCAD (-/-) mouse retina.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY014363-02
Application #
6746846
Study Section
Special Emphasis Panel (ZRG1-VISC (01))
Program Officer
Mariani, Andrew P
Project Start
2003-06-01
Project End
2008-05-31
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
2
Fiscal Year
2004
Total Cost
$245,250
Indirect Cost
Name
Johns Hopkins University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Rattner, Amir; Toulabi, Leila; Williams, John et al. (2008) The genomic response of the retinal pigment epithelium to light damage and retinal detachment. J Neurosci 28:9880-9