Abstract

The hypothesis of the project is that there are distinctive domains and motifs for the retinal GABA receptor that determine the subunit-subunit assembly, composition and biophysical function of the GABAR in the retina. To test this hypothesis, three specific aims are proposed: (1) coexpression of the GABA-rho subunit with the subunits of the GABA-A family will be used to define the unique assembly behavior of the retinal GABA subunit and compatibility of subunit-subunit assembly will be determined by their biophysical and pharmacological characteristics; (2) chimeric subunits will be built to define the portions of the primary sequence necessary for co-assembly and to test this with in vitro translation and yeast two-hybrid approaches; and (3) the substitution of smaller portions of the sequence and mutagenesis will be used to further investigate the residues responsible for the subunit-subunit interactions of the retinal GABA-rho subunits.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY011653-01A1
Application #
2398099
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1998-07-01
Project End
2001-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Wright State University
Department
Physiology
Type
Schools of Medicine
DUNS #
City
Dayton
State
OH
Country
United States
Zip Code
45435

  Publications

Zheng, Wei; Xie, Wenrui; Zhang, Jianhua et al. (2003) Function of gamma-aminobutyric acid receptor/channel rho 1 subunits in spinal cord. J Biol Chem 278:48321-9
Ekema, George M; Zheng, Wei; Lu, Luo (2002) Interaction of GABA receptor/channel rho(1) and gamma(2) subunit. Invest Ophthalmol Vis Sci 43:2326-33
Lu, L; Reinach, P S; Kao, W W (2001) Corneal epithelial wound healing. Exp Biol Med (Maywood) 226:653-64
Xu, D; Wang, L; Olson, J E et al. (2001) Asymmetrical response of p38 kinase activation to volume changes in primary rat astrocytes. Exp Biol Med (Maywood) 226:927-33
Kang, S S; Wang, L; Kao, W W et al. (2001) Control of SV-40 transformed RCE cell proliferation by growth-factor-induced cell cycle progression. Curr Eye Res 23:397-405
Kang, S S; Li, T; Xu, D et al. (2000) Inhibitory effect of PGE2 on EGF-induced MAP kinase activity and rabbit corneal epithelial proliferation. Invest Ophthalmol Vis Sci 41:2164-9
Wang, L; Zhou, P; Craig, R W et al. (1999) Protection from cell death by mcl-1 is mediated by membrane hyperpolarization induced by K(+) channel activation. J Membr Biol 172:113-20
Wang, L; Xu, D; Dai, W et al. (1999) An ultraviolet-activated K+ channel mediates apoptosis of myeloblastic leukemia cells. J Biol Chem 274:3678-85
Xu, D; Wang, L; Dai, W et al. (1999) A requirement for K+-channel activity in growth factor-mediated extracellular signal-regulated kinase activation in human myeloblastic leukemia ML-1 cells. Blood 94:139-45
Lu, L; Huang, Y (1998) Separate domains for desensitization of GABA rho 1 and beta 2 subunits expressed in Xenopus oocytes. J Membr Biol 164:115-24