This proposal is based on recent findings from the applicant's lab indicating that the PDE inhibitory subunit, gamma, plays important regulatory roles in phototransduction that had not been previously recognized. In particular, the applicant and his colleagues have shown that the PDE- gamma subunit is phosphorylated and ADP-ribosylated. Experiments are proposed that will further define the roles of phosphorylation and ADP- ribosylation. The kinase and ADP-ribosyltransferase that modify PDE- gamma are to be purified and characterized. Additional experiments are proposed to investigate the mechanism(s) that regulate the rate of hydrolysis of GTP by transducin.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY009631-07
Application #
2459139
Study Section
Special Emphasis Panel (ZRG1-VISC (01))
Project Start
1991-08-01
Project End
1999-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
7
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Wayne State University
Department
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
Yamazaki, Akio; Nishizawa, Yuji; Matsuura, Isao et al. (2013) Microtubule-associated protein tau in bovine retinal photoreceptor rod outer segments: comparison with brain tau. Biochim Biophys Acta 1832:1549-59
Yamazaki, Akio; Hayashi, Fumio; Matsuura, Isao et al. (2011) Binding of cGMP to the transducin-activated cGMP phosphodiesterase, PDE6, initiates a large conformational change involved in its deactivation. FEBS J 278:1854-72
Yamazaki, Akio; Tatsumi, Masahiro; Bondarenko, Vladimir A et al. (2010) Mechanism for the regulation of mammalian cGMP phosphodiesterase6. 2: isolation and characterization of the transducin-activated form. Mol Cell Biochem 339:235-51
Yamazaki, Akio; Bondarenko, Vladimir A; Matsuura, Isao et al. (2010) Mechanism for the regulation of mammalian cGMP phosphodiesterase6. 1: identification of its inhibitory subunit complexes and their roles. Mol Cell Biochem 339:215-33
Bondarenko, Vladimir A; Hayashi, Fumio; Usukura, Jiro et al. (2010) Involvement of rhodopsin and ATP in the activation of membranous guanylate cyclase in retinal photoreceptor outer segments (ROS-GC) by GC-activating proteins (GCAPs): a new model for ROS-GC activation and its link to retinal diseases. Mol Cell Biochem 334:125-39
Yamazaki, Akio; Yamazaki, Matsuyo; Yamazaki, Russell K et al. (2006) Illuminated rhodopsin is required for strong activation of retinal guanylate cyclase by guanylate cyclase-activating proteins. Biochemistry 45:1899-909
Yamazaki, Matsuyo; Usukura, Jiro; Yamazaki, Russell K et al. (2005) ATP binding is required for physiological activation of retinal guanylate cyclase. Biochem Biophys Res Commun 338:1291-8
Yamazaki, Akio; Yu, Hao; Yamazaki, Matsuyo et al. (2003) A critical role for ATP in the stimulation of retinal guanylyl cyclase by guanylyl cyclase-activating proteins. J Biol Chem 278:33150-60
Kajimura, Naoko; Yamazaki, Matsuyo; Morikawa, Kosuke et al. (2002) Three-dimensional structure of non-activated cGMP phosphodiesterase 6 and comparison of its image with those of activated forms. J Struct Biol 139:27-38
Desmeules, Philippe; Grandbois, Michel; Bondarenko, Vladimir A et al. (2002) Measurement of membrane binding between recoverin, a calcium-myristoyl switch protein, and lipid bilayers by AFM-based force spectroscopy. Biophys J 82:3343-50

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