A possible role of RGS9 in phototransduction. A bridge between the cGMP-phosphodiesterase system and the guanylyl cyclase system.
In the current concept of phototransduction, the concentration of cGMP in retinal rod outer segments is controlled by the balance of two enzyme activities: cGMP phosphodiesterase (PDE) and guanylyl cyclase (GC). However, no protein directly mediates these two enzyme systems. Here we show that RGS9, which is suggested to control PDE activity through regulation of transducin GTPase activity (He, W., Cowan, C. W., and Wensel, T. G. (1998) Neuron 20, 95-102), directly interacts with GC. When proteins in the Triton X-100-insoluble fraction of bovine rod outer segments were isolated by two-dimensional gel electrophoresis and binding of GC to these proteins was examined using a GC-specific antibody, proteins (55 and 32 kDa) were found to interact with GC. However, the activity of GC bound to the 55-kDa protein was not detected. This observation was elucidated by the finding that the 55-kDa protein inhibited GC activity in a dose-dependent manner. Amino acid sequence showed that five peptides derived from the 55-kDa protein were identical to corresponding peptides of RGS9. Together with other biochemical characterization of the 55-kDa protein, these observations indicate that the 55-kDa protein is RGS9 and that RGS9 inhibits GC. RGS9 may serve as a mediator between the PDE and GC systems.
Graduate School of Science and Technology, Faculty of Science, Kobe University, Nada, Kobe 657, Japan.
K
K
Seno
A
A
Kishigami
S
S
Ihara
T
T
Maeda
V A
VA
Bondarenko
Y
Y
Nishizawa
J
J
Usukura
A
A
Yamazaki
F
F
Hayashi
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D020690:GTPase-Activating Proteins; D006162:Guanylate Cyclase / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D012374:Rod Cell Outer Segment / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D020690:GTPase-Activating Proteins; D011506:Proteins; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006162:Guanylate Cyclase