The beta 2 adrenergic receptor (B2AR) is one of the pharmacologically best characterized cell surface receptors. A serotype-specific receptor for the type 3 mammalian reovirus (ReoVR) has a similar cellular specificity and appears to be structurally related to the B2AR. In this project, recently isolated genomic and cDNA clones of the mouse B2AR will be characterized. Binding studies of the cloned B2AR protein and of the protein altered by site-directed mutagenesis and deletion will be performed to map the catecholamine and reovirus binding sites. The developmental expression of the B2AR/ReoVR will be studied using antibody probes for the receptor protein and molecular probes for the mRNA which encodes it. The timing, anatomic distribution, and cellular specificity of expression in developing rat brain will be determined using tissue sections and in primary neuronal and glial cultures. The functional effects of anti-ReoVR antibody binding on oligodendrocytes will be determined in an in vitro culture system and in vivo. In the last year of the project, studies of the molecular mechanisms regulating B2AR gene expression will be initiated, including attempts to isolate the regulatory regions of the gene. These studies will yield information at both the molecular and cellular levels concerning an important hormone/neurotransmitter receptor and virus receptor. Also, fundamental information concerning the developmental biology of this receptor in the nervous system will be obtained. Finally, insight into a potentially important pathogenetic mechanism of demyelinating disease will be obtained.
|Arai, M; Cohen, J A (1994) Subcellular localization of the F5 protein to the neuronal membrane-associated cytoskeleton. J Neurosci Res 38:348-57|
|Arai, M; Cohen, J A (1993) Characterization of the neuroimmune protein F5: localization to the dendrites and perikarya of mature neurons and the basal aspect of choroid plexus epithelial cells. J Neurosci Res 36:305-14|
|Cohen, J A; Baggott, L A; Romano, C et al. (1993) Characterization of a mouse beta 1-adrenergic receptor genomic clone. DNA Cell Biol 12:537-47|
|Cohen, J A; Arai, M; Prak, E L et al. (1992) Characterization of a novel mRNA expressed by neurons in mature brain. J Neurosci Res 31:273-84|
|Rubin, D H; Wetzel, J D; Williams, W V et al. (1992) Binding of type 3 reovirus by a domain of the sigma 1 protein important for hemagglutination leads to infection of murine erythroleukemia cells. J Clin Invest 90:2536-42|
|Arai, M; Prystowsky, M B; Cohen, J A (1992) Expression of the T-lymphocyte activation gene, F5, by mature neurons. J Neurosci Res 33:527-37|