Establishment of the uniquely specific cell-cell interactions required in nervous systems almost certainly requires the participation of unique cell surface components. The ability of neuronal cells to distinguish themselves from others, migrate to specific sites, and elaborate specialized functional connections is likely to be related to the synthesis and expression of complex arrays of cell membrane-associated macromolecules. While cell surface constituents must play important roles in establishing cellular identity and in regulating specific cell-cell interactions, relatively little is known concerning the biochemical nature of such molecules or their mechanism of action. During recent studies of the binding of fluorescein-conjugated lectins to developing mouse retina, it was observed that peanut lectin (PNA) binds specifically to cone photoreceptors cells. The binding is most intense in the cone outer segment region and in discrete, possible synaptic, regions of the inner and outer plexiform layers of the retina. These results indicate the existence of significant cellular and regional hetero-geneity in the distribution of glycoconjugate molecules within the retina, and suggest the possibility that PNA-binding glycoproteins might be employed as specific molecular markers for cone photoreceptors and their synapses. The proposed studies will examine a possible role for PNA-binding molecules in establishing the biochemical basis of neuronal specificity in the retina. The molecules responsible for the cone-specific binding of PNA in the retina will be characterized biochemically and purified by lectin affinity chromatography. Specific polyclonal and monoclonal antibodies directed against specific PNA-binding glycoproteins will be developed and used to monitor the expression of specific molecular species during cellular differentiation and synaptogenesis in the retina. Ultrastructural studies will identify the cellular and subcellular correlates of PNA binding. The results of these studies should provide new data of significance in our understanding of the molecular and genetic basis of neural cell development of function.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004741-03
Application #
3259204
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1983-04-01
Project End
1986-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90033
Tombran-Tink, J; Shivaram, S M; Chader, G J et al. (1995) Expression, secretion, and age-related downregulation of pigment epithelium-derived factor, a serpin with neurotrophic activity. J Neurosci 15:4992-5003
Hageman, G S; Marmor, M F; Yao, X Y et al. (1995) The interphotoreceptor matrix mediates primate retinal adhesion. Arch Ophthalmol 113:655-60
Blanks, J C; Johnson, L V; Hageman, G S (1993) Stage-specific binding of peanut agglutinin to aggregates of degenerating photoreceptor cells in the rd mouse retina. Exp Eye Res 57:265-73
Johnson, L V; Hageman, G S (1991) Structural and compositional analyses of isolated cone matrix sheaths. Invest Ophthalmol Vis Sci 32:1951-7
Tombran-Tink, J; Johnson, L V (1989) Neuronal differentiation of retinoblastoma cells induced by medium conditioned by human RPE cells. Invest Ophthalmol Vis Sci 30:1700-7
Johnson, L V; Blanks, J C; Hageman, G S (1989) Effects of retinal degenerations on the cone matrix sheath. Prog Clin Biol Res 314:217-32
Tombran-Tink, J; Johnson, L V (1989) Collagen-induced alterations in intercellular adhesion and antigen expression in retinoblastoma cells. Exp Eye Res 48:549-59
Blanks, J C; Hageman, G S; Johnson, L V et al. (1988) Ultrastructural visualization of primate cone photoreceptor matrix sheaths. J Comp Neurol 270:288-300
Johnson, L V; Hageman, G S (1988) Characterization of molecules bound by the cone photoreceptor-specific monoclonal antibody CSA-1. Invest Ophthalmol Vis Sci 29:550-7
Hageman, G S; Johnson, L V (1987) Chondroitin 6-sulfate glycosaminoglycan is a major constituent of primate cone photoreceptor matrix sheaths. Curr Eye Res 6:639-46

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