RHODOPSIN STRUCTURE AND ENVIRONMENT IN VISION

视觉中的视紫红质结构和环境

• 批准号: 2158783
• 负责人: ARLENE Diane ALBERT
• 金额: $ 19.06万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-05-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2158783
• 关键词: Amphibia; Urodela; age difference; alternatives to animals in research; animal tissue; cell age; cholesterol; cone cell; digitonin; eye regeneration; fatty acids; laboratory rat; membrane biogenesis; membrane lipids; nuclear magnetic resonance spectroscopy; phosphodiesterases; phospholipids; phosphorylation; photoactivation; protein structure; retina; rhodopsin; rod cell; thermostability; transducin; vision; visual photosensitivity

The rod cells of vertebrate retinas are responsible for vision at low levels of light. Rod outer segment disks are stacked along the length of the outer segment. The disks are formed from evaginations of the plasma membrane at the base of the outer segment. They are displaced toward the apical Lip as new disks are formed. The disk membranes can now be separated as a function of their cholesterol content using sucrose density gradients. High levels of membrane cholesterol are associated with newly synthesized disks. Both the phospholipid headgroup and the total fatty acid composition remains essentially constant among the disks as they age. Thus the major change observed in the lipid composition of disk membranes as they are apically displaced is a decrease in the membrane cholesterol content. However new disks and plasma membrane differ significantly in phospholipid composition. This suggests that an important sorting process occurs at disk formation. By completing the lipid and protein analysis of plasma membrane and of disks as a function of age we will obtain some understanding of this interesting sorting process. It is possible that these sorting processes are impaired or altered in disease states. Therefore these studies will be extended to other animals, including a comparison of normal and dystrophic rats. The visual pigment, rhodopsin, is an integral membrane protein of the disks and functions in the primary event of visual transduction. Rhodopsin initiates a cascade of events which culminates in the hydrolysis of cGMP and the closure of the plasma membrane Na+ channels. The membrane cholesterol composition is capable of modulating this membrane activity. In particular the loss of cholesterol from the disk membrane would appear, from preliminary data to increase the potential response to light. Therefore the dependence of membrane activity on cholesterol will be examined in greater detail during this project period. The effect of cholesterol on rhodopsin properties such as photolysis, regeneration and thermal stability will be investigated. It is anticipated that this information will provide insight with respect to the mechanism of the cholesterol effect. Finally, the possibility that cholesterol may be responsible, at least in part, for the significantly reduced sensitivity of some cones cells, relative to rod cells, will be investigated. Cone cells in which the "disks" are not separated from the plasma membrane do not have the opportunity to move the photopigments to a reduced cholesterol environment with its apparently increased sensitivity to light.

脊椎动物视网膜的杆细胞负责低处的视力 光的水平。 杆外段磁盘沿着长度堆叠 外部段。 这些磁盘是由等离子体的逃避形成的 膜位于外部段的底部。 他们朝向 形成新磁盘的顶唇。 磁盘膜现在可以 使用蔗糖分离作为其胆固醇含量的函数 密度梯度。 高水平的膜胆固醇是相关的 具有新合成的磁盘。 磷脂头组和 磁盘中总脂肪酸组成基本上保持恒定 随着年龄的增长。 因此，在脂质组成中观察到的主要变化 磁盘膜由于顶端流离失所是降低的 膜胆固醇含量。 但是新磁盘和质膜 磷脂成分有显着差异。 这表明 重要的分类过程发生在磁盘形成。 通过完成 质膜和磁盘作为功能的脂质和蛋白质分析 年龄，我们将对这种有趣的分类有所了解 过程。 这些分类过程可能受到损害或 疾病状态改变。 因此，这些研究将扩展到 其他动物，包括正常和营养不良大鼠的比较。 视觉色素，视紫红质，是不可或缺的膜蛋白 在视觉转导的主要事件中磁盘和功能。 Rhodopsin发起了一系列事件，最终达到 CGMP的水解和质膜Na+通道的闭合。 膜胆固醇成分能够调节这一点 膜活动。 特别是盘中胆固醇的损失 膜将出现，从初步数据来增加潜力 对光的反应。 因此，膜活性对 胆固醇将在此项目期间更详细地检查 时期。 胆固醇对视紫红质特性（例如 将研究光解，再生和热稳定性。 它 预计此信息将提供有关 胆固醇作用的机制。 最后，有可能 胆固醇可能至少部分负责 相对于杆细胞，某些锥细胞的敏感性降低将是 调查。 “磁盘”没有与之分离的锥细胞 质膜没有机会将光鲜摄入移至 胆固醇环境降低，显然增加了 对光的敏感性。