Cell Biology of Signaling Complexes in Phototransduction

光转导信号复合物的细胞生物学

• 批准号: 7127826
• 负责人: SUSAN L TSUNODA
• 金额: $ 3.7万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7127826
• 关键词: Drosophilidae; biological signal transduction; cell biology; confocal scanning microscopy; electron microscopy; gene expression; gene mutation; genetic screening; immunocytochemistry; mutant; photoconduction; protein protein interaction; receptor; southern blotting; transcription factor

DESCRIPTION (provided by applicant): An important issue in the field of signal transduction is how signaling molecules are organized into different pathways within the same cell. Our goal is to understand how the signal transduction cascade that underlies the phototransduction process is organized, and how individual components interact and participate in normal visual function. The importance of assembling signaling molecules into architecturally defined complexes has emerged as an essential cellular strategy to ensure speed and specificity of signaling. Results in Drosophila photoreceptors as well as in other systems and organisms have further demonstrated that the subcellular localization of these signaling complexes is essential for effective signaling. Mislocalization of signaling components is often the equivalent of their absence, and consequences can be severe. Critical questions that arise then are: how are signaling complexes targeted to the right subcellular domain? How and where are they assembled? How is this assembly regulated? How are they anchored or stabilized in the proper locale? This grant proposal focuses on a molecular-genetic dissection of the assembly and localization of signaling complexes in Drosophila photoreceptors. We will 1) perform a comprehensive genetic screen to isolate mutations affecting the proper localization of signaling complexes in photoreceptors, 2) characterize the mutants genetically, cell biologically, and physiologically, 3) isolate the defective genes, compare the homologous sequence from wild-type flies, identify the nature of the change, and introduce the wild-type gene back into flies and test for rescue of the phenotype, 4) for those genes that warrant further investigation, we will study how the proteins they encode function in assembly and localization processes. Components and strategies used in Drosophila are likely to be conserved in mammals. We expect to identify and characterize key components in the assembly, regulation of assembly, targeting, and anchoring of signaling complexes.

描述（由申请人提供）： 信号转导领域的一个重要问题是信号分子如何在同一细胞内组织成不同的途径。我们的目标是了解光转导过程中的信号转导级联是如何组织的，以及各个组件如何相互作用并参与正常的视觉功能。将信号分子组装成结构定义的复合物的重要性已成为确保信号传导速度和特异性的基本细胞策略。果蝇光感受器以及其他系统和生物体的结果进一步证明，这些信号复合物的亚细胞定位对于有效的信号传导至关重要。信号元件的错误定位通常相当于它们的缺失，后果可能很严重。接下来出现的关键问题是：信号复合物如何靶向正确的亚细胞结构域？它们如何以及在哪里组装？这个集会是如何监管的？它们如何锚定或稳定在适当的位置？该资助提案的重点是对果蝇光感受器中信号复合物的组装和定位进行分子遗传学剖析。我们将 1) 进行全面的遗传筛选，以分离影响光感受器中信号复合物正确定位的突变，2) 从遗传、细胞生物学和生理学角度表征突变体，3) 分离缺陷基因，比较野生型的同源序列果蝇，确定变化的性质，并将野生型基因引入果蝇并测试表型的拯救，4）对于那些值得进一步研究的基因，我们将研究它们编码的蛋白质如何在组装和本地化流程。果蝇中使用的成分和策略可能在哺乳动物中是保守的。我们期望识别和表征信号复合物的组装、组装调节、靶向和锚定中的关键组件。