MOLECULAR ANALYSIS OF PHOTOTRANSDUCTION

我们有兴趣更深入地了解这些组件和 光传导级联的调节和了解微扰如何 在感光细胞生理学上导致各种形式的视网膜 退化。我们使用果蝇视觉系统来检查这些广泛的 问题。果蝇对分子、电生理和 识别分子和在体内研究蛋白质的遗传学方法 生化途径中的关系。因为许多无脊椎动物的视觉 转导蛋白具有脊椎动物的同源物，两个级联蛋白都可能发挥作用 以类似的方式。因此，分子和分子的识别 果蝇的机制可能阐明脊椎动物的视觉传导 路径。许多视觉转导分子表现为视网膜变性 在无脊椎动物或脊椎动物身上发生改变时。因此，学习 这些分子在视觉传导中的作用将阐明 导致退化的机制。 我们将扩展我们对果蝇视网膜变性-B(RdgB)的分析， 它表现出光感受器的光依赖性退化。RDGB 蛋白质是一种新的磷脂酰肌醇转移蛋白(PI-TP)所必需的 在视觉传导级联中。PI-TPS的一个定义角色是 囊泡运输的调控。RDgB蛋白的免疫定位 与横纹肌胞浆面附近的蛋白质一致 在囊泡从跨高尔基体到 横纹肌。RdgB多克隆抗血清染色脊椎动物杆状内壁 片段，这表明脊椎动物的“光感受器”同源基因存在。 果蝇分子的详细分析和果蝇的鉴定 脊椎动物同源物可以解释杆状外盘组装和 可能是一种新型的视网膜变性。 Dgq基因编码两个果蝇光感受器特异的G蛋白a 亚基、DGq1和DGq2。我们从基因和生物化学方面证明了 DGq1参与了光激活途径。进一步分析 将揭示什么是DGq1的S效应分子以及DGq2在 光传导级联。此外，一种类似的显性突变 DGq1和转导蛋白均导致大鼠脑内异常适应反应 果蝇和小白鼠。因此，进一步的遗传和 DGq1的分子分析可能阐明一种常见的适应机制 脊椎动物和无脊椎动物。

We are interested in a deeper understanding of the components and regulation of the phototransduction cascade and learning how perturbations in photoreceptor cell physiology lead to various forms of retinal degeneration. We use the Drosophila visual system to examine these broad questions. Drosophila is amenable to molecular, electrophysiological, and genetic approaches to identify molecules and to study in vivo the protein relationships in biochemical pathways. Because many invertebrate visual transduction proteins have vertebrate homologs, both cascades may function in an analogous manner. Thus, the identification of molecules and mechanisms in Drosophila may clarify the vertebrate visual transduction pathway. Many visual transduction molecules exhibit retinal degeneration when altered in either invertebrates or vertebrates. Therefore, studying the role of these molecules in visual transduction will elucidate the mechanisms leading to degeneration. We will extend our analysis of Drosophila retinal degeneration-B (rdgB), which exhibits light-dependent degeneration of photoreceptors. The rdgB protein is a novel phosphatidylinositol transfer protein (PI-TP) required in the visual transduction cascade. One defined role for PI-TPs is regulation of vesicular transport. Immunolocalization of the rdgB protein near the cytosolic face of the rhabdomeres is consistent with the protein functioning in vesicular transport from a trans-Golgi compartment to the rhabdomeres. The rdgB polyclonal antiserum stains vertebrate rod inner segments, suggesting that a vertebrate "photoreceptor" homolog exists. Detailed analysis of the Drosophila molecule and identification of the vertebrate homolog could elucidate aspects of rod outer disc assembly and possibly a novel form of retinal degeneration. The dgq gene encodes two Drosophila photoreceptor-specific G-protein a subunits, DGq1 and DGq2. We demonstrated genetically and biochemically that DGq1 is involved in the light-activated pathway. Further analyses will reveal what is DGq1 's effector molecule and the role of DGq2 in the phototransduction cascade. In addition, an analogous dominant mutation in both DGq1 and transducin leads to an abnormal adaptation response in Drosophila and mouse, respectively. Therefore, further genetic and molecular analyses of DGq1 may elucidate a common adaptation mechanism in both vertebrates and invertebrates.