The interactions of photoreceptor membranes with the signal-coupling protein transducin are being studied in order to gain a deeper understanding of the roles of membranes and proteins bound to them in intracellular signal transduction. Visual signal transduction has in common with many other intracellular communication processes that it is mediated by peripheral proteins at the surface of membranes, as well as integral membrane proteins. In vision, the GTP-binding protein transducin shuttles between photoexcited rhodopsin (the primary signal receptor, an integral membrane protein) and cGMP phosphodiesterase (the target effector enzyme, a peripheral membrane protein). Transducin can be solubilized under mild conditions, but it requires the disk membrane to carry out its functions. An understanding of the underlying principles controlling membrane-association in the normal functioning of cellular regulators like transducin and other g-proteins should facilitate an understanding of the pathological conditions that arise when this normal regulation becomes disrupted by disease. A major emphasis is the characterization of a recently discovered subpopulation of transducin (Tm) that is much more potent than the major population in stimulating cyclic-GMS phosphodiesterase, and is much more tightly bound in the GTP form. This coexistence of membrane-bound activity, and to purify and characterize the protein(s) responsible for this activity. In addition, the membrane interactions of the major soluble population of transducin (Tm) will be studied in depth. These experiments will employ membrane binding assays, phosphodiesterase activation measurements and fluorescent probes to determine equilibrium and kinetic properties of Ts interactions with disk membranes and other proteins bound to them. Analysis of these interactions is essential in order to understand the function of this protein, and to compare its functional properties to those of Tm. This understanding should provide insight into the physiological modes of action of these proteins, and into the mechanisms by which G-proteins transduce signals in other cell types as well.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY007981-03
Application #
3265071
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1989-08-01
Project End
1992-07-31
Budget Start
1991-08-01
Budget End
1992-07-31
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
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