Regulation of sensitivity in vertebrate rod photoreceptors by calcium
Regulation of sensitivity in vertebrate rod photoreceptors by calcium
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钙对脊椎动物视杆光感受器敏感性的调节
DOI：
10.1016/0166-2236(96)89624-x
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发表时间：
1996
影响因子：
15.9
通讯作者：
K. Yau
中科院分区：
文献类型：
--
作者：
Y. Koutalos;K. Yau
Fig. 1.视杆细胞中的光转导。(A)视杆细胞。图中显示了视杆细胞对光的整体反应。详情见正文。(6)视杆细胞中的光转导示意图。符号说明：GCAP，鸟苷酸环化酶激活蛋白; hu，光子; Rh，视紫红质; Rh *，光活化视紫红质; Rh'-P，Rh * 的磷酸化形式;+，刺激或正调节;-，抑制或负调节。改编自参考文献8。由通过cGMP门控通道的流入和通过涉及细胞外Na+与细胞内Ca+和K+交换的转运机制的流出组成（参考文献1和13）。在光照下，cGMP门控通道的关闭停止了Ca "的内流，但外流继续，降低了外段""中游离Ca"的浓度。Ca *+的这种减少触发了导致光适应的负反馈。事实上，如果通过最小化外节中Ca 2+浓度的变化来在很大程度上去除Ca 2+介导的反馈，则视杆（和视锥）几乎不显示对背景照明的任何主动适应。虽然Ca *+作为光适应介质的作用已经被接受了一段时间，但其潜在机制直到最近才被解开。已经发现了几种Ca '+介导的反馈途径。首先，合成cGMP的鸟苷酸环化酶被Ca+抑制，使得当Ca+浓度在光中降低时，鸟苷酸环化酶活性增加，这抵消了cGMP的光刺激水解。Ca的这种作用"多年来一直为人所知"，但它首先由Koch和Stryer定量，他们表明Ca的生理浓度以协同方式调节酶。此外，这些作者发现，一种可溶性因子激活了该酶，并介导了Ca '的抑制作用。这些发现在很大程度上得到了随后的生物化学Z '-2和电生理学的证实。实验最近，可溶性因子被纯化并克隆了编码它的基因。该因子是一种具有特征性EF-手形基序的26-kDa Ca "结合蛋白，并被命名为鸟苷酸环化酶激活蛋白或GCAP（参考文献28，29，33）。当通过贴片移液管引入到杆的分离的外节中时，GCAP加速细胞从光的恢复。第二反馈途径涉及光刺激的磷酸二酯酶活性。早期的实验“已经表明这种活动被Ca增强”，但最令人信服的证据来自Kawamura和Murakami最近的工作。这种作用由另一种Ca+结合蛋白介导，称为恢复蛋白或S-调节蛋白，其显然通过在高浓度Ca ++下抑制活化视紫红质的磷酸化而起作用（参考文献36 - 45）。因此，高浓度的Ca2+延长了光激发的视紫红质的寿命，这导致大量转导素分子的活化，从而导致更大的光刺激磷酸二酯酶活性。相反，当光中Ca-福尔斯的浓度下降时，光激发的视紫红质的寿命降低，这导致较低的磷酸二酯酶活性。当经由贴片移液管将恢复蛋白输注到杆的分离的外节段中时，其导致光响应的延长，这与其如上所述的作用一致。除了恢复素介导的作用之外，Lagnado和Baylor最近还描述了Ca在光转导途径中的单独作用，其同样导致在降低的Ca 2+浓度下光转导的较低放大。介导这种效应的因素目前尚不清楚。最后，cGMP门控...
Fig. 1. Phototransduction in rod cells.(A) Rod photoreceptor cell. Diagram showing the overall response of the rod cell to light. See text for details.(6) Scheme of phototransduction in rods. Symbols: GCAP, guonylate cyclase-activating protein; hu, photon; Rh, rhodopsin; Rh*, photoactivated rhodopsin; Rh’-P, phosphoryfated form of Rh*;+, stimulation or positive modulation;-, inhibition or negative modulation. Adapted from Ref. 8. consists of an influx through the cGMP-gated channels and an efflux through a transport mechanism that involves the exchange of extracellular Na’with intracellular Ca*+ and K+(Refs l&13). In the light, the closure of the cGMP-gated channels stops the influx of Ca”, but the efflux continues, reducing the concentration of free Ca” in the outer segment”“‘. This decrease in Ca*+ triggers a negative feedback that results in light adaptation. Indeed, if the Ca’+-mediated feedback is largely removed by minimizing changes in the concentration of Ca2+ in the outer segment, rods (and cones) show hardly any active adaptation to background illumination’y-2~. While the role of Ca*+ as a mediator of light adaptation has been accepted for some time, the underlying mechanisms have become unraveled only recently. Several Ca’+-mediated feedback pathways have been discovered. First, guanylate cyclase, which synthesizes cGMP, is inhibited by Ca*+, so that when the concentration of Ca” decreases in the light the guanylate cyclase activity increases, which counteracts the light-stimulated hydrolysis of cGMP. This action of Ca” has been known for many years”, but it was first quantified by Koch and Stryer”‘, who showed that physiological concenirations of Ca” modulated the enzyme in a cooperative manner. In addition, these authors found that a soluble factor activated the enzyme and also mediated the inhibitory action of Ca’.. These findings have largely been confirmed by subsequent biochemicalZ’-2s and electrophysiological”‘-.” experiments. Recently, the soluble factor was purified and the gene that encodes it cloned. The factor is a 26-kDa Ca”-binding protein with characteristic EF-hand motifs, and has been named the guanylate cyclaseactivating protein, or GCAP (Refs 28, 29, 33). When introduced into an isolated outer segment of a rod through a patch pipette, GCAP speeds up the cell’s recovery from light”‘.A second feedback pathway involves the lightstimulated phosphodiesterase activity. Early experiments” had suggested that this activity is enhanced by Ca”, but the most convincing evidence came from the recent work of Kawamura and Murakami”. This effect is mediated by another Ca’+-binding protein, called recoverin or S-modulin, which apparently acts by inhibiting the phosphorylation of activated rhodopsin at high concentrations of Ca*’(Refs 36-45). Thus, high concentrations of Ca” prolong the lifetime of photoexcited rhodopsin, which leads to the activation of a larger number of transducin molecules and hence greater light-stimulated phosphodiesterase activity. Conversely, when the concentration of Ca” falls in the light, the lifetime of photoexcited rhndopsin decreases, which results in lower phosphodiesterase activity. When recoverin is infused into an isolated outer segment of a rod via a patch pipette, it leads to a prolongation of the light response, which is consistent with its role as described above”‘. In addition to the recoverin-mediated effect, Lagnado and Baylor”’have recently described a separate effect of Ca” in the phototransduction pathway that likewise leads to a lower amplification of phototransduction at decreased concentrations of Ca2+. The factor that mediates this effect is currently unknown. Finally, the cGMP-gated …
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视紫红质是光感受器视杆外节中蛋白激酶 C 的主要原位底物。
DOI：
--
发表时间：
1993
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Newton,AC;Williams,DS
通讯作者：
Williams,DS
牛视杆光感受器环 GMP 磷酸二酯酶的磷酸化。
DOI：
10.1042/bj2950049
发表时间：
1993
期刊：
The Biochemical journal
影响因子：
--
作者：
Udovichenko,IP;Cunnick,J;Gonzales,K;Takemoto,DJ
通讯作者：
Takemoto,DJ
G 蛋白不经三磷酸鸟苷水解即可使视觉转导失活。
DOI：
10.1126/science.1519062
发表时间：
1992
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Erickson,MA;Robinson,P;Lisman,J
通讯作者：
Lisman,J
牛视杆细胞感光细胞中磷酸蛋白对视网膜 cGMP 级联的调节。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Lee,RH;Ting,TD;Lieberman,BS;Tobias,DE;Lolley,RN;Ho,YK
通讯作者：
Ho,YK