Phagocytosis and fluid transport in the retinal pigment epithelium (RPE) are necessary for visual processing and survival of the photoreceptors. The long-term goal of this proposed study is to understand the molecular regulation of these processes. The applicant has identified a novel G protein- coupled receptor, epithelium neuropeptide receptor (ENPR). Its sequence is most closely related to neuropeptide receptors, especially that for neuropeptide Y. Transcripts encoding ENPR are present in the RPE and ciliary body; they are not present in other tissues, with the exception of the brain. This restricted pattern of expression suggests that ENPR controls a unique G protein-coupled pathway important to the specialized functions of the RPE. The applicant proposes to perform functional characterization of the novel receptor ENPR in order to the test the hypothesis that ligand activation regulates RPE phagocytosis and fluid transport. These studies will include structural characterization of the human gene, analysis of cellular and subcellular localization, identification of the native ligand, G-protein partners, and second messengers. The elucidation of ENPR receptor function and signaling pathways may allow better understanding of how ENPR activation is translated into physiological responses of the RPE required for normal functioning of the photoreceptors.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Visual Sciences C Study Section (VISC)
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University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
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Ammar, D A; Thompson, D A (2000) Human type 2 neuropeptide Y receptor gene. Isolation and characterization. Methods Mol Biol 153:25-43
Ammar, D A; Hughes, B A; Thompson, D A (1998) Neuropeptide Y and the retinal pigment epithelium: receptor subtypes, signaling, and bioelectrical responses. Invest Ophthalmol Vis Sci 39:1870-8
Nicoletti, A; Kawase, K; Thompson, D A (1998) Promoter analysis of RPE65, the gene encoding a 61-kDa retinal pigment epithelium-specific protein. Invest Ophthalmol Vis Sci 39:637-44
Thompson, D A; Othman, M I; Lei, Z et al. (1998) Localization of receptors for luteinizing hormone/chorionic gonadotropin in neural retina. Life Sci 63:1057-64
Gu, S M; Thompson, D A; Srikumari, C R et al. (1997) Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy. Nat Genet 17:194-7
Lutz, C M; Frankel, W N; Richards, J E et al. (1997) Neuropeptide Y receptor genes on human chromosome 4q31-q32 map to conserved linkage groups on mouse chromosomes 3 and 8. Genomics 41:498-500
Lutz, C M; Richards, J E; Scott, K L et al. (1997) Neuropeptide Y receptor genes mapped in human and mouse: receptors with high affinity for pancreatic polypeptide are not clustered with receptors specific for neuropeptide Y and peptide YY. Genomics 46:287-90
Ammar, D A; Eadie, D M; Wong, D J et al. (1996) Characterization of the human type 2 neuropeptide Y receptor gene (NPY2R) and localization to the chromosome 4q region containing the type 1 neuropeptide Y receptor gene. Genomics 38:392-8
Tal, M; Ammar, D A; Karpuj, M et al. (1995) A novel putative neuropeptide receptor expressed in neural tissue, including sensory epithelia. Biochem Biophys Res Commun 209:752-9
Nicoletti, A; Wong, D J; Kawase, K et al. (1995) Molecular characterization of the human gene encoding an abundant 61 kDa protein specific to the retinal pigment epithelium. Hum Mol Genet 4:641-9