A possible role of RGS9 in phototransduction - A bridge between the cGMP-phosphodiesterase system and the guanylyl cyclase system

被引:27
作者
Seno, K
Kishigami, A
Ihara, S
Maeda, T
Bondarenko, VA
Nishizawa, Y
Usukura, J
Yamazaki, A
Hayashi, F [1 ]
机构
[1] Kobe Univ, Fac Sci, Dept Biol, Kobe, Hyogo 657, Japan
[2] Kobe Univ, Grad Sch Sci & Technol, Kobe, Hyogo 657, Japan
[3] Wayne State Univ, Sch Med, Dept Ophthalmol, Detroit, MI 48201 USA
[4] Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA
[5] Wayne State Univ, Sch Med, Kresge Eye Inst, Detroit, MI 48201 USA
[6] Nagoya Univ, Sch Med, Dept Anat, Nagoya, Aichi 466, Japan
关键词
D O I
10.1074/jbc.273.35.22169
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:22169 / 22172
页数:4
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