Interaction of retinal guanylate cyclase with the alpha subunit of transducin: potential role in transducin localization.
Interaction of retinal guanylate cyclase with the alpha subunit of transducin: potential role in transducin localization.
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视网膜鸟苷酸环化酶与转导蛋白α亚基的相互作用：在转导蛋白定位中的潜在作用。
DOI：
10.1042/bj20081513
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Slepak,VladlenZ
中科院分区：
文献类型：
--
作者：
Rosenzweig,DerekH;Nair,KSaidas;Levay,Konstantin;Peshenko,IgorV;Crabb,JohnW;Dizhoor,AlexanderM;Slepak,VladlenZ
脊椎动物的光转导是由cGMP介导的，cGMP由retGC（视网膜鸟苷酸环化酶）产生并由cGMP磷酸二酯酶降解。光通过G蛋白转导素刺激cGMP水解，G蛋白转导素直接结合并激活磷酸二酯酶。明亮的光线也会导致转导蛋白从视杆细胞的OS（外节）重新定位到内部隔室。在本研究中，我们展示了以前未知的Gαt（transducin α亚基）和retGC之间的相互作用的实验证据。Gα t与来自视网膜或来自共转染的COS-7细胞的retGC共免疫沉淀。retGC-Gα t复合物也存在于视锥细胞中。这种相互作用也发生在缺乏RGS 9（G蛋白信号调节因子9）的小鼠中，RGS 9是一种先前显示与Gα t和retGC都相关的蛋白质。Gαt-retGC相互作用主要由retGC的激酶同源结构域介导，其与GDP结合的Gα t的结合强于GTP[S]（GTPγS;鸟苷5′-[γ-硫代]三磷酸）形式。Gα t和Gβγ均不影响retGC介导的cGMP合成，无论是否存在GCAP（鸟苷酸环化酶激活蛋白）和Ca 2+。在retGC-1基因敲除小鼠中，光依赖性转导素从OS向内节的再分布速率显著加快，而在黑暗开始后转导素向OS的迁移被延迟。用cGMP补充透化的光感受器不影响转导蛋白的易位。总之，这些结果表明，Gα t和retGC之间的蛋白质-蛋白质相互作用代表了一种新的机制，调节视杆细胞光依赖性转导的移位。
Vertebrate phototransduction is mediated by cGMP, which is generated by retGC (retinal guanylate cyclase) and degraded by cGMP phosphodiesterase. Light stimulates cGMP hydrolysis via the G-protein transducin, which directly binds to and activates phosphodiesterase. Bright light also causes relocalization of transducin from the OS (outer segments) of the rod cells to the inner compartments. In the present study, we show experimental evidence for a previously unknown interaction between Gαt(the transducin α subunit) and retGC. Gαtco-immunoprecipitates with retGC from the retina or from co-transfected COS-7 cells. The retGC–Gαtcomplex is also present in cones. The interaction also occurs in mice lacking RGS9 (regulator of G-protein signalling 9), a protein previously shown to associate with both Gαtand retGC. The Gαt–retGC interaction is mediated primarily by the kinase homology domain of retGC, which binds GDP-bound Gαtstronger than the GTP[S] (GTPγS; guanosine 5′-[γ-thio]triphosphate) form. Neither Gαtnor Gβγaffect retGC-mediated cGMP synthesis, regardless of the presence of GCAP (guanylate cyclase activating protein) and Ca2+. The rate of light-dependent transducin redistribution from the OS to the inner segments is markedly accelerated in the retGC-1-knockout mice, while the migration of transducin to the OS after the onset of darkness is delayed. Supplementation of permeabilized photoreceptors with cGMP does not affect transducin translocation. Taken together, these results suggest that the protein–protein interaction between Gαtand retGC represents a novel mechanism regulating light-dependent translocation of transducin in rod photoreceptors.
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RGS9-1 N 末端抑制视网膜鸟苷酸环化酶。
DOI：
10.1006/bbrc.2001.5346
发表时间：
2001
期刊：
Biochemical and biophysical research communications.
影响因子：
--
作者：
Yu,H;Bondarenko,VA;Yamazaki,A
通讯作者：
Yamazaki,A
DOI：
10.1073/pnas.93.2.560
发表时间：
1996-01-23
影响因子：
11.1
作者：
Baylor, D
通讯作者：
Baylor, D
ROD 光感受器中存在亮氨酸-甘氨酸-天冬氨酸重复序列富集蛋白 (LGN)，它是转导蛋白的假定结合伴侣。
影响因子：
4.4
作者：
Nair,KSaidas;Mendez,Ana;Blumer,JoeB;Rosenzweig,DerekH;Slepak,VladlenZ
通讯作者：
Slepak,VladlenZ
影响因子：
--
作者：
U. Wolfrum;A. Giessl;A. Pulvermüller
通讯作者：
U. Wolfrum;A. Giessl;A. Pulvermüller
影响因子：
4.8
作者：
Yang, RB;Garbers, DL
通讯作者：
Garbers, DL